Role of IVIG in the Treatment of Autoimmune Conditions With Concurrent Immune Checkpoint Inhibitors for Metastatic Cancer
In this report, we discuss a case in which a patient with metastatic renal cell carcinoma experienced exacerbation of underlying paraneoplastic dermatomyositis after treatment with ICI. He was successfully continued on ICI with the use of intravenous immunoglobulin. The patient experienced adequate control of his myositis but also experienced deepening of his antitumor response. (Source: Journal of Immunotherapy)
Source: Journal of Immunotherapy - September 7, 2021 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

Immune Checkpoint Inhibitor–associated Diarrhea and Colitis: A Systematic Review and Meta-analysis of Observational Studies
The objective of our systematic review and meta-analysis was to determine the incidence and outcomes of ICI-associated diarrhea and colitis. Bibliographic databases were searched through August 13, 2019, for observational studies of ICI therapy reporting the incidence and/or treatment of diarrhea or colitis. The primary outcome was ICI-associated diarrhea and colitis. Meta-analyses were performed with random-effects models. Twenty-five studies (N=12,661) were included. All studies had a high risk of bias in at least 1 domain. The overall incidence of diarrhea/colitis was 12.8% [95% confidence interval (CI), 8.8–18.2,...
Source: Journal of Immunotherapy - September 7, 2021 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

Molecular and Immune Correlates of PDCD1 (PD-1), PD-L1 (CD274), and PD-L2 (PDCD1LG2) DNA Methylation in Triple Negative Breast Cancer
Immune checkpoints are important targets in oncological therapy. Recent studies have proven efficacy of immune checkpoint inhibition (ICI) in treatment of triple negative breast cancer (TNBC). However, only a proportion of TNBC-patients benefit from ICI. Thus, current scientific efforts in this context are focused on the identification of a robust biomarker that enables patient stratification. In the present study, we investigated the epigenetic regulation of PD-1 (PDCD1), PD-L1 (CD274), and PD-L2 (PDCD1LG2). Methylation data of PD-1, PD-L1, and PD-L2, and complex immunogenomic data were obtained from The Cancer Genome Atl...
Source: Journal of Immunotherapy - September 7, 2021 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

Long-term Overall Survival and Predictors in Anti–PD-1-naive Melanoma Patients With Brain Metastases Treated With Immune Checkpoint Inhibitors in the Real-world Setting: A Multicohort Study
Long-term survival outcomes among melanoma patients with brain metastases treated with immune checkpoint inhibitors are limited. In this retrospective study at 2 centers, metastatic melanoma patients with radiographic evidence of brain metastases who received anti–programmed death-1 (PD-1) monotherapy or nivolumab in combination with ipilimumab between 2014 and 2017 were included. Overall survival (OS) was assessed in diagnosis-specific graded prognostic assessment (ds-GPA) and melanoma–molecular graded prognostic assessment (molGPA) prognostic risk groups. Baseline clinical covariates were used to identify pre...
Source: Journal of Immunotherapy - September 7, 2021 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

Potent, Selective CARs as Potential T-Cell Therapeutics for HPV-positive Cancers
Next-generation T-cell therapies will likely continue to utilize T-cell receptors (TCRs) and chimeric antigen receptors (CARs) because each receptor type has advantages. TCRs often possess exceptional properties even when tested unmodified from patients’ T cells. CARs are generally less sensitive, possibly because their ligand-binding domains are grafted from antibodies selected for binding affinity or avidity and not broadly optimized for a functional response. Because of the disconnect between binding and function among these receptor types, the ultimate potential of CARs optimized for sensitivity and selectivity i...
Source: Journal of Immunotherapy - September 7, 2021 Category: Allergy & Immunology Tags: Basic Studies Source Type: research

Inhibition of Polyamine Biosynthesis Using Difluoromethylornithine Acts as a Potent Immune Modulator and Displays Therapeutic Synergy With PD-1-blockade
Polyamines are known to play a significant role in cancer progression and treatment using difluoromethylornithine (DFMO), an inhibitor of polyamine biosynthesis, has shown some clinical promise. It is interesting to note that, while DFMO is directly cytostatic in vitro, recent work has suggested that it achieves its antitumor efficacy in vivo by enhancing adaptive antitumor immune responses. On the basis of these data, we hypothesized that DFMO might act as an immune sensitizer to increase tumor responsiveness to checkpoint blockade. To test this hypothesis, we treated tumors with DFMO, in either the presence or absence of...
Source: Journal of Immunotherapy - September 7, 2021 Category: Allergy & Immunology Tags: Basic Studies Source Type: research

Immune Checkpoint Inhibitor–related Guillain-Barré Syndrome: A Case Series and Review of the Literature
We present 3 cases of ICI-related GBS; review cases described in current literature, and discuss treatment strategies. Three patients developed GBS after ICI treatment. The first case with pembrolizumab had a fatal outcome despite treatment with multiple regimens, including steroids and intravenous immunoglobulin (IVIg). The other 2 cases with nivolumab-induced and pembrolizumab-induced GBS, respectively, responded well to treatment with IVIg and steroids. In the current literature, a total of 31 other cases were found. Treatment for ICI-related GBS mostly consisted of concurrent IVIg and steroids (44%), which led to clini...
Source: Journal of Immunotherapy - August 19, 2021 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

A Phase I Study of an IDO-1 Inhibitor (LY3381916) as Monotherapy and in Combination With an Anti-PD-L1 Antibody (LY3300054) in Patients With Advanced Cancer
This study explored the safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity of LY3381916 monotherapy and in combination with a programmed death-ligand 1 (PD-L1) inhibitor (LY3300054) in patients with advanced solid tumors. During dose escalation, patients received escalating doses of LY3381916 at 60–600 mg once daily (qd) and 240 mg twice daily in monotherapy (n=21) and in combination with PD-L1 inhibitor at 700 mg every 2 weeks (n=21). A modified toxicity probability interval method was used to guide dose escalation. Dose-limiting toxicities occurred in 3 patients; 1...
Source: Journal of Immunotherapy - August 19, 2021 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

Myeloid Cell Infiltration Correlates With Prognosis in Cholangiocarcinoma and Varies Based on Tumor Location
In conclusion, the CC TIME is a heterogenous milieu highly infiltrated by innate and adaptive immune cells, which differs based on primary tumor location and between primary tumors and metastatic lesions. The correlation of intratumoral M2 macrophages and myeloid cells with a worse prognosis may suggest promising immunotherapeutic targets in CC. (Source: Journal of Immunotherapy)
Source: Journal of Immunotherapy - August 19, 2021 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

Pretreatment Eosinophil Counts in Patients With Advanced or Metastatic Urothelial Carcinoma Treated With Anti-PD-1/PD-L1 Checkpoint Inhibitors
Eosinophils influence antitumor immunity and may predict response to treatment with immune checkpoint inhibitors (ICIs). To examine the association between blood eosinophil counts and outcomes in patients with advanced or metastatic urothelial carcinoma (mUC) treated with ICIs, we identified 2 ICI-treated cohorts: discovery (n=60) and validation (n=111). Chemotherapy cohorts were used as comparators (first-line platinum-based chemotherapy, n=75; second-line or more pemetrexed, n=77). The primary endpoint was overall survival (OS). Secondary endpoints were time on treatment (ToT) and progression-free survival. Univariate an...
Source: Journal of Immunotherapy - August 19, 2021 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

Encephalitis Induced by Durvalumab During Treatment of Metastatic Small-Cell Lung Cancer: Illustrative Case and Review of the Literature
This report describes a 66-year-old female who received Durvalumab for metastatic small-cell lung cancer. Following 3 cycles of treatment, she developed encephalitis. (Source: Journal of Immunotherapy)
Source: Journal of Immunotherapy - August 19, 2021 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

Risk Factors for Relapse after Intentional Discontinuation of Immune Checkpoint Inhibitors in Melanoma Patients
Immune checkpoint inhibitors (ICIs) have tremendously changed the therapeutic landscape of melanoma since they are associated with a durable response, allowing for intentional discontinuation of therapy after complete or partial remission. However, a subset of patients develops a relapse after cessation of ICI treatment and may not respond to reinduction of ICIs. The aim of the present study was to identify risk factors for relapse after intentional discontinuation of ICI therapy. Patients with intentional discontinuation of ICI therapy for metastatic or unresectable melanoma from 5 German university hospitals were analyze...
Source: Journal of Immunotherapy - June 10, 2021 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

Immune Checkpoint Inhibition in Marjolin Ulcer: A Case Series
We describe the clinicopathologic features and clinical outcomes of our MU-SCC cohort. (Source: Journal of Immunotherapy)
Source: Journal of Immunotherapy - June 10, 2021 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

Pembrolizumab Utilization and Clinical Outcomes Among Patients With Advanced Melanoma in the US Community Oncology Setting: An Updated Analysis
Favorable outcomes have been observed with pembrolizumab among patients with advanced melanoma in clinical trials; however, limited evidence exists on the long-term efficacy in the real-world setting. This was an updated, retrospective observational study of adult patients with advanced (unresectable or metastatic) melanoma who initiated pembrolizumab (in any line of therapy) between January 1, 2014, and December 31, 2016, in The US Oncology Network and were followed through December 31, 2019 [median follow-up: 18.2 mo (range: 0.1–63.1 mo)]. Study data were sourced from electronic health records. Patien...
Source: Journal of Immunotherapy - June 10, 2021 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

PMEL as a Prognostic Biomarker and Negatively Associated With Immune Infiltration in Skin Cutaneous Melanoma (SKCM)
Premelanosome protein (PMEL) is crucial for the formation of melanosomal fibrils through the transition from stage I to stage II melanosomes. It was used as a target antigen in some adoptive T-cell therapy of melanoma. The correlation of PMEL to prognosis and immune cell infiltration level are unknown in melanoma. The PMEL expression was evaluated via Tumor Immune Estimation Resource, Oncomine and Gene Expression Profiling Interactive Analysis (GEPIA). We also evaluate the influence of PMEL on overall survival via GEPIA, PrognoScan, and immunohistochemistry in human tissue microarray. The correlation between PMEL expressio...
Source: Journal of Immunotherapy - June 10, 2021 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

The Intracellular Domain of CD40 is a Potent Costimulatory Element in Chimeric Antigen Receptors
The costimulatory domains incorporated into second-generation and third-generation chimeric antigen receptors (CARs) strongly influence CAR-T-cell function. Here, we explored second-generation and third-generation CARs harboring the signaling domain of the CD40 receptor as a new costimulatory element in comparison with similar CARs carrying the 4-1BB domain. In CARs of both generations, CD40 was more potent than 4-1BB in triggering the NF-κB signaling pathway. In human T cells from 2 donors, CD40 was comparable to 4-1BB in upregulating costimulatory and activation markers, inducing proinflammatory cytokine secretion ...
Source: Journal of Immunotherapy - June 10, 2021 Category: Allergy & Immunology Tags: Basic Study Source Type: research

Encephalitis Associated With Immune Checkpoint Inhibitor Treatment in Patients With Melanoma
Since the approval of immune checkpoint anti–programmed cell death protein 1 antibodies (pembrolizumab and nivolumab) and anti–cytotoxic T-lymphocyte–associated protein 4 (ipilimumab) in combination or monotherapy, significant advances have been made in the treatment of metastatic melanoma. The nonspecific immune stimulation resulting from these drugs can case a wide range of side effects in many organs including the nervous system, named immune-related adverse events. Few immune-related encephalitis associated with these antibodies have been described in the literature. It is a rare complication ( (Sourc...
Source: Journal of Immunotherapy - May 20, 2021 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

Immunotherapy Utilization Among Patients With Metastatic NSCLC: Impact of Comorbidities
In patients with metastatic non–small cell lung cancer (mNSCLC), the extent to which immunotherapy utilization rate varies by comorbidities is unclear. Using the National Cancer Database from 2015 to 2016, we assessed the association between levels of comorbidity and immunotherapy utilization among mNSCLC patients. Burden of comorbidities was ascertained based on the modified Charlson-Deyo score and categorized as an ordinal variable (0, 1, and ≥2). Immunotherapy utilization was determined based on registry data. Multivariable logistic regressions were used to estimate adjusted odds ratios (aOR) and 95% confidence...
Source: Journal of Immunotherapy - May 20, 2021 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

Sudden Otovestibular Dysfunction in 3 Metastatic Melanoma Patients Treated With Immune Checkpoint Inhibitors
We describe detailed diagnostic work-up and therapeutic interventions and discuss possible pathogenic mechanisms of this rare and disabling event. (Source: Journal of Immunotherapy)
Source: Journal of Immunotherapy - May 20, 2021 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

Baseline Plasma Inflammatory Profile Is Associated With Response to Neoadjuvant Chemotherapy in Patients With Pancreatic Adenocarcinoma
Despite its increased application in pancreatic ductal adenocarcinoma (PDAC), complete response to neoadjuvant therapy (NAT) is rare. Given the critical role of host immunity in regulating cancer, we sought to correlate baseline inflammatory profiles to significant response to NAT. PDAC patients receiving NAT were classified as responders (R) or nonresponders (NR) by carbohydrate antigen 19-9 response, pathologic tumor size, and lymph node status in the resected specimen. Baseline (treatment-naive) plasma was analyzed to determine levels of 27 inflammatory mediators. Logistic regression was used to correlate individual med...
Source: Journal of Immunotherapy - May 20, 2021 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

Cancer Therapeutics–related Cardiac Dysfunction in Patients Treated With Immune Checkpoint Inhibitors: An Understudied Manifestation
The widespread use of immune checkpoint inhibitors (ICI) has become a mainstay of care for a variety of malignancies. However, these therapies portend a range of adverse effects, including a potentially fatal form of cardiotoxicity which to date has not been elucidated. We aimed to evaluate the baseline characteristics of ICI-mediated cardiotoxicity. We performed a retrospective study evaluating patients treated with ICI who performed at least 2 echocardiography examinations, before and after the initiation of ICI. Cardiotoxicity was defined as Cancer Therapeutics-related Cardiac Dysfunction (CTRCD) development, with an ab...
Source: Journal of Immunotherapy - May 20, 2021 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

A Multicentre Retrospective Analysis of Toxicity in 6-weekly Versus 3-weekly Pembrolizumab
We present real-world comparative toxicity data. Patients receiving pembrolizumab for any indication between March and December 2019 were included across 3 regional centers. Toxicity data were collected retrospectively using Common Terminology Criteria for Adverse Events, v5.0. Clinically significant immune-related adverse events (CSirAE) were defined as immune-related events and grade ≥3 rash. Data were analyzed using incidence (Poisson distribution) and incidence ratio. Overall, 63 patients started on q6w and 110 patients received q3w. There were 3 (q6w) and 8 (q3w) grade 3–5 CSirAE and 13 (q6w) and 31 (q3w) gra...
Source: Journal of Immunotherapy - April 16, 2021 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

Impact of Baseline Corticosteroids on Immunotherapy Efficacy in Patients With Advanced Melanoma
This is a 2-center, retrospective study which aimed to evaluate the effect of baseline corticosteroid use on immunotherapy efficacy in patients with advanced melanoma. We included all patients with advanced unresectable and metastatic melanoma on single-agent programmed cell death protein 1 (PD-1) inhibitors at the Cancer Centre of Southeastern Ontario and London Regional Cancer Program. We defined baseline corticosteroid use as prednisone-equivalent of ≥10 mg within 30 days of immunotherapy initiation. Our study had 166 patients in total, and 25 were taking corticosteroids at the initiation of the PD-1 inhibitor...
Source: Journal of Immunotherapy - April 16, 2021 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

Anti-PD1 Immunotherapy for Metastatic Renal Cancer Boosted Humoral Immunity In a Hemodialysis Patient
Immune checkpoint inhibitors by blocking specific inhibitory pathways induce T-cell-mediated tumor lysis. However, many remain to be elucidated about their effect on human humoral immunity. We evaluated the effect of the PD1 inhibitor nivolumab on humoral immunity by following the levels of antibodies against hepatitis B surface antigen (anti-HBs) in a hemodialysis patient successfully vaccinated against hepatitis B virus 5 years ago and now starting nivolumab for renal cell carcinoma lung metastases. Anti-HBs kinetics after administration of an extra vaccine dose were also evaluated. Nivolumab increased anti-HBs and facil...
Source: Journal of Immunotherapy - April 16, 2021 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

Cardiac Troponin I and T in Checkpoint Inhibitor–associated Myositis and Myocarditis
Checkpoint inhibitor–associated myocarditis (ir-myocarditis) and myositis (ir-myositis) may occur concurrently among patients on checkpoint inhibitor immunotherapy. While cardiac-specific troponin I (cTnI) and troponin T (cTnT) are regarded to have similar sensitivities and specificities in conditions such as acute coronary syndrome, the cardiac specificity of cTnT has been challenged following observation that patients with neuromuscular diseases, including myositis, may have elevated cTnT without apparent clinical evidence of myocardial injury. Consequently, in the context of concurrent ir-myositis, cTnI may be a m...
Source: Journal of Immunotherapy - April 16, 2021 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

Branched Multipeptide-combined Adjuvants Potentially Improve the Antitumor Effects on Glioblastoma
The promising immunotherapy effects of a multiple antigenic peptide on glioblastoma (GBM) in a previous study encourage the use of adjuvants to enhance its therapeutic efficacy. Among adjuvants, pan HLA-DR-binding epitope (PADRE) and anti-programmed cell death protein 1 (anti-PD1) have potentially been tested for cancer immunotherapy. Therefore, here we evaluated the ability of PADRE and anti-PD1 to enhance the function of the branched multipeptide against GBM. The potential utility of tumor-associated antigens (ErbB-2 and WT-1) targeting GBM with HLA-A24 was confirmed and a branched multipeptide was constructed from these...
Source: Journal of Immunotherapy - April 16, 2021 Category: Allergy & Immunology Tags: Basic Studies Source Type: research

Identification of HLA-A*0201-restricted CTL Epitopes for MLAA-34-specific Immunotherapy for Acute Monocytic Leukemia
Our previous research has shown that monocytic leukemia–associated antigen-34 (MLAA-34) was a novel antiapoptotic molecule with unique expression in acute monocytic leukemia (M5), making it an ideal target for T-cell–based immunotherapy. Here, we sought to identify HLA-A*0201-restricted cytotoxic T-lymphocyte (CTL) epitope of MLAA-34 by reverse immunology. In all, 10 HLA-A*0201 restricted epitopes of MLAA-34 were predicted by bioinformatics. MLAA-34324–332, MLAA-34293–301, and MLAA-34236–244 showed the strongest HLA-A*0201-binding affinity. The percentages of HLA-A*0201-MLAA-34236–244 te...
Source: Journal of Immunotherapy - April 16, 2021 Category: Allergy & Immunology Tags: Basic Studies Source Type: research

Hepatitis B Virus Reactivation in Cancer Patients Treated With Immune Checkpoint Inhibitors
There have been unique adverse events reported with targeted blockade of programmed death-1 (PD-1), programmed death-ligand-1 (PD-L1), and cytotoxic T-lymphocyte-associated protein-4 (CTLA4), including immune mediated toxicities. Recently, there have been reports of hepatitis B reactivation (HBVr) occurring with PD-1/PD-L1 inhibitors, which may result in treatment delays, interruptions, or discontinuation. This retrospective literature review and analysis of the Food and Drug Administration’s (FDA) Adverse Events Reporting System (FAERS) queried reported cases of “Hepatitis B reactivation” reported with t...
Source: Journal of Immunotherapy - March 18, 2021 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

Incidence and Prediction of Immune Checkpoint Inhibitor-related Nephrotoxicity
Immune checkpoint inhibitors (ICIs) may cause immune-related adverse events that can affect any organ system, including the kidneys. Our study aimed to better characterize the incidence of and predictive factors for immune-related acute kidney injury (irAKI) and evaluate steroid responsiveness. An institutional database (Carolina Data Warehouse) was queried for patients who received ICIs and subsequently had substantial AKI, defined as a doubling of baseline creatinine. A retrospective chart review was performed to determine the cause of AKI. AKI events determined to be immune-related were further analyzed. A total of 1766...
Source: Journal of Immunotherapy - March 18, 2021 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

Carpal Tunnel Syndrome: A New Adverse Effect of Immune Checkpoint Inhibitors, 11 Cases
This study aims at reporting 11 cases of carpal tunnel syndrome (CTS) occurring in patients on immunotherapy. The increasing use of immune checkpoint inhibitors in oncodermatology is associated with the appearance of immunologic adverse effects linked to nonspecific stimulation of the immune system. CTS has not been reported in this context. A retrospective multicenter review was performed on CTSs occurring on immunotherapy and confirmed with electroneuromyography. Data were collated from patients’ files. Most of the time, CTS was severe, bilateral, with a motor deficit and confirmed axonal damage on electroneuromyog...
Source: Journal of Immunotherapy - March 18, 2021 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

Checkpoint Inhibitor-associated Cutaneous Small Vessel Vasculitis: A Review of the Literature
Checkpoint inhibitor therapy is an established cancer treatment option often complicated by the development of immune-related adverse events. Vasculitis has been reported with a broad spectrum of both cutaneous and systemic manifestations and can be complicated by delayed diagnosis. The authors report 2 histologically proven cases of cutaneous leucocytoclastic vasculitis induced by programmed cell-death 1 inhibitor inhibitor nivolumab. As physicians, including medical oncologists and dermatologists, we need to be aware of this clinical entity and the importance of clinicopathological confirmation in this setting to confirm...
Source: Journal of Immunotherapy - March 18, 2021 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

Immune Checkpoint Inhibitor-induced Bilateral Vestibulopathy
We present a severe case of CPI-related ongoing and most likely irreversible bilateral vestibular affection. A 59-year-old male melanoma patient with brain metastasis undergoing immunotherapy with anti-cytotoxic T-lymphocyte antigen-4 and anti-programmed death-1 antibodies developed severe debilitating rotatory vertigo. Bilateral vestibulopathy was diagnosed as a result of the CPI therapy after a thorough analysis including magnetic resonance imaging, laboratory tests of blood and cerebrospinal fluid as well as neurological and otorhinolaryngology examinations. The vertigo improved slightly during a 10-day course of steroi...
Source: Journal of Immunotherapy - March 18, 2021 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

Development of a Tetravalent T-Cell Engaging Bispecific Antibody Against Glypican-3 for Hepatocellular Carcinoma
Cancer therapies benefit from accelerated development of biotechnology, and many immunotherapeutic strategies spring up including vaccines, the immune checkpoint blockade, chimeric antigen receptor T cells, and bispecific antibodies (BsAbs). Glypican-3 (GPC3) is a member of the heparan sulfate proteoglycan family of proteins and is highly expressed in hepatocellular carcinoma (HCC) cell membranes. Here, the authors describe a new tetravalent BsAb h8B-BsAb targeting GPC3 and CD3 antigens and studied its antitumor activities against HCC. h8B-BsAb was designed based on immunoglobulin G with a fragment variable fused to the li...
Source: Journal of Immunotherapy - March 18, 2021 Category: Allergy & Immunology Tags: Basic Studies Source Type: research

Re-examination of MAGE-A3 as a T-cell Therapeutic Target
In 2013, an innovative MAGE-A3-directed cancer therapeutic of great potential value was terminated in the clinic because of neurotoxicity. The safety problems were hypothesized to originate from off-target T-cell receptor activity against a closely related MAGE-A12 peptide. A combination of published and new data led us to test this hypothesis with current technology. Our results call into question MAGE-A12 as the source of the neurotoxicity. Rather, the data imply that an alternative related peptide from EPS8L2 may be responsible. Given the qualities of MAGE-A3 as an onco-testis antigen widely expressed in tumors and larg...
Source: Journal of Immunotherapy - March 18, 2021 Category: Allergy & Immunology Tags: Basic Studies Source Type: research

Case Report and Review of 7 Similar Cases in the Literature: Cutaneous Sarcoidosis as Side Effect of Pembrolizumab Plus Chemotherapy in Stage IV Squamous Cell Carcinoma of Lung
We present an unusual case of cutaneous sarcoidosis in a 63-year-old white female who was diagnosed with stage IV squamous cell lung cancer developed skin manifestations 3 months after started chemo/pembrolizumab. Sarcoidosis was confirmed by skin punch biopsy and resolved after a short course of systemic glucocorticoid while maintained on pembrolizumab with lower frequency. These sarcoid-like lesions associated with the blockage of programmed death receptor-1 have been increasingly described in many different malignancies especially in melanoma. There is a need for further investigation to the characterization of the popu...
Source: Journal of Immunotherapy - February 1, 2021 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

Cardiovascular Toxicity and Mortality Associated With Adoptive Cell Therapy and Tumor-infiltrating Lymphocytes for Advanced Stage Melanoma
Adoptive cellular therapy (ACT) with tumor-infiltrating lymphocytes (TILs) has emerged as an effective treatment option for unresectable stage III/IV metastatic melanoma. Acute toxicities, particularly cardiovascular (CV), can have a significant effect on the completion of therapy. We abstracted information on 43 patients who received ACT-TIL treatment for melanoma at the Moffitt Cancer Center between 2010 and 2016. The Student t tests and χ2 tests were used to compare patient characteristics by presence versus absence of specific CV complications. In this cohort, 32.6% developed hypotension requiring treatment with in...
Source: Journal of Immunotherapy - February 1, 2021 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

Effects of Antibiotic Use on Outcomes in Cancer Patients Treated Using Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis
Antibiotic (ATB) use seems to negatively affect the outcomes of immune checkpoint inhibitors (ICIs). The aim of this review is to clarify whether ATB use influences the efficacy of ICI treatment in cancer patients. Databases of MEDLINE, Embase, and Cochrane Library were searched for reports published in English between January 2007 and December 2019. We included studies that compared the outcomes of ATB use and no-ATB use in cancer patients using ICIs. Two reviewers independently selected eligible studies and extracted the data. Meta-analysis was performed with pooling of unadjusted hazard ratios (HRs) for overall survival...
Source: Journal of Immunotherapy - February 1, 2021 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

Primary Biliary Cirrhosis and Granulomatous Hepatitis After Immune Checkpoint Blockade in Patients With Metastatic Melanoma: Report of 2 Cases and Literature Discussion
We present here the case of a 69-year-old man with metastatic melanoma developing a severe primary biliary cirrhosis under pembrolizumab, and of a 52-year-old woman with metastatic melanoma with granulomatous hepatitis in the context of an immune-related multiorgan inflammatory reaction due to ipilimumab and nivolumab. Both cases were in part steroid refractory and required a complex diagnostic assessment and long-term therapeutic management. The liver biopsy was crucial for ensuring a correct diagnosis. Clinicians should be aware of rare liver diseases in the context of increased liver enzymes under immune checkpoint inhi...
Source: Journal of Immunotherapy - February 1, 2021 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

Expanded Tumor-infiltrating Lymphocytes From Soft Tissue Sarcoma Have Tumor-specific Function
Adoptive cell transfer (ACT) with tumor-infiltrating lymphocytes (TILs) can generate durable clinical responses in patients with metastatic melanoma and ongoing trials are evaluating efficacy in other advanced solid tumors. The aim of this study was to develop methods for the expansion of tumor-reactive TIL from resected soft tissue sarcoma to a degree required for the ACT. From 2015 to 2018, 70 patients were consented to an institutional review board–approved protocol, and fresh surgical specimens were taken directly from the operating room to the laboratory. Fragments of the tumor (1 mm3) or fresh tumor dige...
Source: Journal of Immunotherapy - February 1, 2021 Category: Allergy & Immunology Tags: Basic Study Source Type: research

Gutting it Out: Developing Effective Immunotherapies for Patients With Colorectal Cancer
Risk factors for colorectal cancer (CRC) include proinflammatory diets, sedentary habits, and obesity, in addition to genetic syndromes that predispose individuals to this disease. Current treatment relies on surgical excision and cytotoxic chemotherapies. There has been a renewed interest in immunotherapy as a treatment option for CRC given the success in melanoma and microsatellite instable (MSI) CRC. Immunotherapy with checkpoint inhibitors only plays a role in the 4%–6% of patients with MSIhigh tumors and even within this subpopulation, response rates can vary from 30% to 50%. Most patients with CRC do not respon...
Source: Journal of Immunotherapy - February 1, 2021 Category: Allergy & Immunology Tags: Review Article Source Type: research

Safety of Immunotherapy Rechallenge After Immune-related Adverse Events in Patients With Advanced Cancer
This retrospective study aimed to investigate the safety profile of continuing or rechallenging patients with advanced cancer who developed grade≥2 immune-related adverse events (irAEs) on immunotherapy-based regimens. Our study had 25, 20, and 40 patients (N=85) in the Treatment Continuation (TCG), Non-Rechallenge (NRG), and Rechallenge Groups (RG), respectively. Subsequent irAEs recurrence were more common in RG than TCG and NRG (78% vs. 56% vs. 25%, P (Source: Journal of Immunotherapy)
Source: Journal of Immunotherapy - December 13, 2020 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

Prognostic Significance of Tumor-infiltrating Lymphocytes on Survival Outcomes of Patients With Resected Pancreatic Ductal Adenocarcinoma: A Systematic Review and Meta-Analysis
Tumor-infiltrating lymphocytes (TILs) play an important role in mediating treatment response in pancreatic cancer. This meta-analysis investigated the prognostic significance of TIL subsets on overall survival (OS) and disease-free survival (DFS) of patients with pancreatic cancer. Studies were gathered via search of PubMed, Google Scholar, and Cochrane Library databases up to August 1, 2019. Using Review Manager version 5.3.5, pooled hazard ratios and 95% confidence intervals (CIs) were calculated using random or fixed-effects models, depending on the heterogeneity of studies. A total of 11 studies comprising 1760 patient...
Source: Journal of Immunotherapy - December 13, 2020 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

High VISTA Expression Correlates With a Favorable Prognosis in Patients With Colorectal Cancer
In this study, immunohistochemical staining was used to investigate VISTA expression in tissue microarrays from 1434 patients with stage I–III CRC (816 in the exploratory cohort and 618 in the validation cohort). VISTA protein was evaluated separately in tumor cells and tumor-infiltrating immune cells (ICs). The associations between VISTA expression, mismatch repair (MMR) status, and clinicopathologic parameters were analyzed, as was the effect of VISTA on survival. High VISTA expression on ICs (ie, ≥5% staining) was more frequent in patients with N0 stage, T1–2 stage, low tumor grade, high CD8 density, and ...
Source: Journal of Immunotherapy - December 13, 2020 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

Analysis of Risk Factors for Hepatotoxicity Induced by Immune Checkpoint Inhibitors
In conclusion, close monitoring of liver function is recommended, especially in male patients, patients younger than 65 years old, and when there is concomitant use of hepatotoxic drugs including acetaminophen and HMG-CoA reductase inhibitors. (Source: Journal of Immunotherapy)
Source: Journal of Immunotherapy - December 13, 2020 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

Checkpoint Blockade in Melanoma Patients With Underlying Chronic Lymphocytic Leukemia
Chronic lymphocytic leukemia (CLL) is associated with immune dysfunction and an increased risk of melanoma. For patients with metastatic melanoma, immunotherapy with checkpoint blocking antibodies is a standard of care. In patients with concomitant CLL and metastatic melanoma, it is not known whether CLL might influence the antimelanoma efficacy or immune-related toxicities of immune checkpoint blockade. Fifteen patients with locally advanced or metastatic melanoma and a concomitant diagnosis of CLL who received pembrolizumab or ipilimumab with or without nivolumab for the treatment of their melanoma at Memorial Sloan Kett...
Source: Journal of Immunotherapy - December 13, 2020 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

Rapid Identification and Evaluation of Neoantigen-reactive T-Cell Receptors From Single Cells
We present a nonviral and non–next-generation sequencing platform for rapid, and efficient neoantigen-specific TCR identification and evaluation that does not require the use of recombinant cloning techniques. The platform includes an innovative method of TCRα detection using Sanger sequencing, TCR pairings and the use of TCRα/β gene fragments for putative TCR evaluation. Using patients’ samples, we validated and compared our new methods head-to-head with conventional approaches used for TCR discovery. Development of a unique demultiplexing method for identification of TCRα, adaptation of...
Source: Journal of Immunotherapy - December 13, 2020 Category: Allergy & Immunology Tags: Basic Study Source Type: research

Efficacy of Pembrolizumab Monotherapy in Patients With or Without Brain Metastases From Advanced Non–Small Cell Lung Cancer With a PD-L1 Expression ≥50%
The authors conducted a multicenter retrospective study on the outcome of programmed death-ligand 1 tumor proportion score≥50% advanced non–small cell lung cancer patients treated with first-line pembrolizumab according to the presence/absence of brain metastases. A total of 282 patients were included, of whom 56 had brain metastases that were treated with upfront local radiation therapy in 80.3% of cases. The overall response rate was 39.2% and 44.4% in patients with and without brain metastases (P=0.48), respectively, while intracranial response rate and intracranial disease control rate were 67.5% and 85.0%, re...
Source: Journal of Immunotherapy - October 7, 2020 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

Incidence and Risk of Colitis With Programmed Death 1 Versus Programmed Death Ligand 1 Inhibitors for the Treatment of Cancer
Colitis is a major immune-related adverse event associated with programmed death 1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors, but the risk of colitis with PD-1 versus PD-L1 inhibitors is not well characterized. We performed a meta-analysis for the incidence of all grade and grade 3–4 colitis with PD-1 inhibitor (nivolumab, pembrolizumab, and cemiplimab) or PD-L1 inhibitor (atezolizumab, avelumab, and durvalumab) monotherapy using a fixed effects model. We also conducted subgroup meta-analyses of non–small cell lung cancer (NSCLC) or urothelial carcinoma (UC) trials, and a network meta-analysis of ...
Source: Journal of Immunotherapy - October 7, 2020 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

Rapid and Complete Response to Combination Anti-CTLA-4 and Anti-PD-1 Checkpoint Inhibitor Therapy in a Patient With Stage IV Refractory End-stage Epithelioid Sarcoma: A Case Report
In conclusion, combined checkpoint inhibition therapy warrants further study in the salvage setting in patients with epithelioid and other INI1 protein–deficient sarcomas seemingly regardless of prior therapy, extent of disease, and performance status. (Source: Journal of Immunotherapy)
Source: Journal of Immunotherapy - October 7, 2020 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

Pembrolizumab-related Bilateral Ocular Hypotony, Uveitis, Cataracts, Exudative Retinal, and Choroidal Detachments: An Unusual Success Story
We report a rare case of profound bilateral complications treated successfully with oral and intravitreal steroids. To the authors’ knowledge, this has not previously been reported in the literature. Ophthalmologists and oncologists should be aware of the ocular effects of pembrolizumab and be able to identify various complications early. Here, cataract surgery with a steroid implant has been an effective sight-saving intervention. The promising visual outcome makes this an unusual success story. (Source: Journal of Immunotherapy)
Source: Journal of Immunotherapy - October 7, 2020 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research