A Phase I, Open-label, Dose-escalation, and Cohort Expansion Study to Evaluate the Safety and Immune Response to Autologous Dendritic Cells Transduced With AdGMCA9 (DC-AdGMCAIX) in Patients With Metastatic Renal Cell Carcinoma
Expression of carbonic-anhydrase IX (CAIX) in clear cell renal cell carcinoma (RCC) makes it an attractive vaccine target. We developed a fusion-gene construct, granulocyte-macrophage (GM) colony-stimulating factor+CAIX, delivered by an adenoviral vector (Ad) into autologous dendritic cells (DCs) in this phase 1 study. The injected immature DCs were expected to stimulate an antigen-specific immune response against CAIX expressing RCC. Three dose-escalation cohorts (5, 15, and 50×106 cells/administration) were injected intradermally q2wk×3 doses based on a 3+3 design. The primary objective was the safety ...
Source: Journal of Immunotherapy - October 7, 2020 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

TNF-a Is a Potent Stimulator of Tc9-Cell Differentiation
In this study, we found that tumor necrosis factor (TNF)-α promotes Tc9 differentiation in vitro, and the TNF-α-induced Tc9 cells display enhanced cell survival and cell proliferation. More importantly, the TNF-α-induced tumor-specific Tc9 cells have increased antitumor capabilities in vivo. TNF-α activates its downstream signaling through 2 cell surface receptors, TNFR1 and TNFR2. In this study, we found that TNF-α promotes Tc9-cell differentiation through TNFR2, but not TNFR1. Furthermore, we found that TNF-α-TNFR2 activates STAT5 and nuclear factor-κB signaling during Tc9-cell d...
Source: Journal of Immunotherapy - October 7, 2020 Category: Allergy & Immunology Tags: Basic Study Source Type: research

Real-world Outcomes of First-line Anti-PD-1 Therapy for Advanced Melanoma: A Nationwide Population-based Study
The efficacy of anti-programmed death-1 (PD-1) monotherapy for advanced melanoma has been established, but it is unknown to what extent patients benefit in the real world. In this observational study with nationwide population-based data from the Dutch Melanoma Treatment Registry, we analyzed real-world outcomes of first-line anti-PD-1 monotherapy in advanced melanoma patients diagnosed in 2015 to 2016. Overall survival (OS) was estimated with the Kaplan-Meier method. Competing risks analysis was used to estimate probabilities for second-line treatment, with death as competing risk. With a Cox model, the association of fac...
Source: Journal of Immunotherapy - September 9, 2020 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

Oligoprogression After Checkpoint Inhibition in Metastatic Melanoma Treated With Locoregional Therapy: A Single-center Retrospective Analysis
Checkpoint inhibitors (CPIs) have demonstrated a heterogenous spectrum of response and disease progression that may not be fully captured by conventional response criteria, such as a limited degree of progression, known as oligoprogression, which could benefit from local treatment. We retrospectively analyzed data from all patients diagnosed with metastatic melanoma, who received CPI between January 2006 and March 2018 at Royal Marsden. We enrolled 36 patients who experienced progression in a maximum of 3 metastatic sites, after achieving disease control from therapy with CPI, and were radically treated with the locoregion...
Source: Journal of Immunotherapy - September 9, 2020 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

Evaluation of Checkpoint Inhibitors in Cancer Patients With End-stage Renal Disease on Hemodialysis: Case Series and Review of the Literature
Checkpoint inhibitors (CPIs) have become standard of care for multiple types of malignancies and while end-stage renal disease is not a contraindication, these patients are frequently excluded from clinical trials. As a result, there is limited data regarding the safety and efficacy of CPI use in this patient population. In this case series, we report outcomes and adverse events in 8 patients on hemodialysis treated with CPIs. Treatment was overall well-tolerated with adverse events in 3 of 8 (37.5%) patients, with 1 (12.5%) having a grade 4 adverse event, which is comparable to the rate reported in literature for the over...
Source: Journal of Immunotherapy - September 9, 2020 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

TIGIT Can Exert Immunosuppressive Effects on CD8+ T Cells by the CD155/TIGIT Signaling Pathway for Hepatocellular Carcinoma In Vitro
The efficacy of adoptive cellular immunotherapy against cancer cells is limited due to the presence of immunosuppressive cells within the solid tumor microenvironment. The upregulation of certain coinhibitory receptors may lead to exhaustion of the immune effector cells. T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) is an immune inhibitory receptor expressed by regulatory T cells and activated T cells and natural killer cells. The aim of this study was to determine the immunosuppressive effects of CD155/TIGIT signaling on CD8+ T cells of adoptive cellular immunotherapy in hepatocel...
Source: Journal of Immunotherapy - September 9, 2020 Category: Allergy & Immunology Tags: Basic Studies Source Type: research

Novel DNA-based T-Cell Activator Promotes Rapid T-Cell Activation and Expansion
This study describes the development of a novel, highly flexible, soluble DNA-based T-cell activation and expansion platform which alleviates the limitations of current technologies and provides rapid T-cell activation and expansion. (Source: Journal of Immunotherapy)
Source: Journal of Immunotherapy - September 9, 2020 Category: Allergy & Immunology Tags: Basic Studies Source Type: research

Bilateral Vocal Cord Paralysis Due to an Immune-related Adverse Event of Nivolumab: A Case Report
No abstract available (Source: Journal of Immunotherapy)
Source: Journal of Immunotherapy - August 13, 2020 Category: Allergy & Immunology Tags: Letter to the Editor Source Type: research

Encephalitis in a Patient With Melanoma Treated With Immune Checkpoint Inhibitors: Case Presentation and Review of the Literature
After the approval of immune checkpoint inhibitors for the treatment of many solid tumors, a new class of adverse events was recognized through the augmented activation of T cells, known as immune-related toxicities (immune-related adverse events). Encephalitis as an immune-mediated phenomenon is extremely rare, but potentially fatal, and questions remain with regard to its optimal management. Herein, we describe a patient with metastatic melanoma who developed autoimmune encephalitis following treatment with nivolumab plus ipilimumab and present the data concerning clinical features, diagnostic procedure, and therapeutic ...
Source: Journal of Immunotherapy - August 13, 2020 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

Laryngeal Tuberculosis in a Patient on Avelumab for Metastatic Nasopharyngeal Carcinoma
We present a case of a patient with metastatic nasopharyngeal carcinoma treated with avelumab, a programmed cell death-ligand 1 inhibitor with resulting laryngeal TB as the presenting symptom of reactivated TB. The patient required quadruple anti-TB therapy, but developed ongoing sequelae of laryngeal TB, including dysphagia and laryngeal stenosis. Ongoing trials are examining the use of avelumab in head and neck cancer patients with locally advanced disease, recurrent, or metastatic disease. Awareness of the risk of new and reactivated TB is crucial. (Source: Journal of Immunotherapy)
Source: Journal of Immunotherapy - August 13, 2020 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

A Phase I, Dose Escalation, Single Dose Trial of Oral Attenuated Salmonella typhimurium Containing Human IL-2 in Patients With Metastatic Gastrointestinal Cancers
Salmonella has been shown to preferentially colonize solid tumors. It is known that toxicity limits the systemic administration of immunomodulatory cytokines that have a significant anticancer effect. Therefore, we tested a unique cancer treatment strategy comprised of oral delivery of Saltikva, an attenuated strain of Salmonella typhimurium that contain the human gene for interleukin-2. In preclinical experimentation, a significant antitumor effect without toxicity was observed. A dose escalation, single dose, Phase I trial was conducted. Dose escalation (105 to 1010) while monitoring for dose limiting toxicity and respon...
Source: Journal of Immunotherapy - August 13, 2020 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

WT1, PRAME, and PR3 mRNA Expression in Acute Myeloid Leukemia (AML)
In conclusion, it is suggested that vaccine strategies for cancer immunotherapy should comprise different TAA peptides anticipating the diverse TAA expression levels on blasts evolving during the course of disease or treatment. (Source: Journal of Immunotherapy)
Source: Journal of Immunotherapy - June 11, 2020 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

The Prognostic Role of High Blood Cholesterol in Advanced Cancer Patients Treated With Immune Checkpoint Inhibitors
Immune checkpoint inhibitors (ICI) have improved survival in numerous types of cancer. However, a great number of unselected patients still do not respond to ICI. Moreover, there is a need to identify biomarkers that could predict the prognosis of immunotherapy-treated patients. The aim of our study is to evaluate the prognostic value of baseline plasmatic cholesterol levels in metastatic cancer patients treated with immunotherapy. We retrospectively enrolled advanced cancer patients consecutively treated with ICI at our center between October 2013 and October 2018 to correlate the blood cholesterol level before treatment ...
Source: Journal of Immunotherapy - June 11, 2020 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

Advanced Non–Small Cell Lung Cancer Patients With Low Tumor Mutation Burden Might Derive Benefit From Immunotherapy
The aim of this study is to investigate the association between tumor mutation burden (TMB) and survival in non–small cell lung cancer (NSCLC) patients with anti-programmed cell death protein 1 and anti-programmed death-ligand 1 blockade. Two retrospective cohorts and The Cancer Genome Atlas NSCLC data set were included in this study. The restricted cubic spline analysis was used to explore the association between TMB and survival. The cutoff values for TMB were determined by X-tile software. Primary outcomes were overall survival (OS). The associations between TMB and intratumor heterogeneity, number of segments, fr...
Source: Journal of Immunotherapy - June 11, 2020 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

BCMA-targeting Bispecific Antibody That Simultaneously Stimulates NKG2D-enhanced Efficacy Against Multiple Myeloma
B-cell maturation antigen (BCMA) is a highly plasma cell-selective protein expressed on malignant plasma cells of patients with multiple myeloma (MM), and it is a defined therapeutic target. Major histocompatibility complex class I-related chain A (MICA) is frequently expressed in lymphoproliferative malignancies including MM. MICA activates natural killer (NK) cells and costimulates T cells by interaction with its immunoreceptor NK cell receptor G2D (NKG2D). Nonetheless, during full-blown MM, tumor cells promote efficient MICA shedding, which evokes NKG2D internalization and immune suppression. To enhance the directional ...
Source: Journal of Immunotherapy - June 11, 2020 Category: Allergy & Immunology Tags: Basic Study Source Type: research

Expression of Programmed Cell Death Proteins in Kaposi Sarcoma and Cutaneous Angiosarcoma
Not only for cutaneous angiosarcoma (CAS) patients but also for advanced and therapy-refractory patients with classic Kaposi sarcoma (CKS) and human immunodeficiency virus (HIV)-associated Kaposi sarcoma (HIV-KS) there is a high need for more effective treatment modalities. The aim of this work was to study programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) protein expression and related immune parameters in CKS, HIV-KS, and CAS and correlate it with other immunologic parameters and clinical data. Immunohistochemistry was performed on formalin-fixed paraffin-embedded tumor tissue of 19 CKS, 7 HIV-KS,...
Source: Journal of Immunotherapy - May 13, 2020 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

Paraneoplastic Encephalitis and Enteric Neuropathy Associated With Anti-Hu Antibody in a Patient Following Immune-checkpoint Inhibitor Therapy
This article reports a case of paraneoplastic encephalitis and enteric neuropathy associated with anti-Hu antibody in a patient with advanced small cell lung cancer. Symptoms presented in the third week after the second dose of sintilimab therapy and manifested as focal seizures and intestinal pseudo-obstruction. The patient’s neurological symptoms improved significantly after treatment with intravenous infusion of methylprednisolone and sequential oral prednisone. This is the first report of sintilimab-related neurological adverse events. On the basis of this case, we speculate that ICIs may induce PNSs. Identifying...
Source: Journal of Immunotherapy - May 13, 2020 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

Study on the Expression Levels and Clinical Significance of PD-1 and PD-L1 in Plasma of NSCLC Patients
This study provides a reference for the assessment of prognosis and risk stratification for NSCLC patients, as well as for immune treatment of cancer. (Source: Journal of Immunotherapy)
Source: Journal of Immunotherapy - May 13, 2020 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

A Case of Response to Immunotherapy in a Patient With MSI Metastatic Colorectal Cancer and Autoimmune Disease Receiving Steroid Therapy
We present the case of a 74-year-old man with pulmonary autoimmune intersitiopathy and microsatellite instability metastatic colorectal cancer who responded to nivolumab despite the concomitant steroid therapy. Furthermore, his autoimmune disease did not worsen during immunotherapy. (Source: Journal of Immunotherapy)
Source: Journal of Immunotherapy - May 13, 2020 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

Successful Treatment of In-Transit Metastatic Melanoma in a Renal Transplant Patient With Combination T-VEC/Imiquimod Immunotherapy
We present a case of in-transit metastatic melanoma in a renal transplant patient. The patient was initially managed with talimogene laherparepvec (T-VEC) injections alone with continued local progression. Addition of topical imiquimod 5% cream to intralesional T-VEC resulted in a rapid and dramatic response, with complete clearance of the cutaneous in-transit metastases and without any sign of organ rejection. In solid organ transplant patients who lack surgical options and are not eligible for treatment with a BRAF inhibitor, and for whom treatment with checkpoint inhibitors present risk of organ rejection, T-VEC either ...
Source: Journal of Immunotherapy - April 10, 2020 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

Complete Recovery of Immune Checkpoint Inhibitor–induced Colitis by Diverting Loop Ileostomy
We present a case of recurrent episodes of checkpoint inhibitor–induced colitis and subsequent Fournier gangrene that resolved after ileostomy formation. Once the Fournier gangrene and colitis had resolved, the ileostomy was reversed. However, within only 4 days, another serious flare-up of colitis occurred, necessitating emergent re-formation of the ileostomy. Expertise in the management of side effects of immune checkpoint inhibitor therapy is currently limited. Although most side effects are mild to moderate and transient, a minority of patients suffer from life-threatening complications, such as colitis. The crea...
Source: Journal of Immunotherapy - April 10, 2020 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

Positive Status of Epstein-Barr Virus as a Biomarker for Gastric Cancer Immunotherapy: A Prospective Observational Study
Immunotherapy has exhibited promising but controversial results in gastric cancer; determining criteria for choosing the appropriate target population is still problematic. Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC) exhibits distinctive genomic aberrations and clinicopathologic features, the positive status of EBV is a potential biomarker. We prospectively recruited 9 patients who were diagnosed with stage-IV EBVaGC, and all of the patients were treated by immune-checkpoint inhibitors. The median age of the patients was 62 years old. The clinicopathologic characteristics demonstrated a male predominance...
Source: Journal of Immunotherapy - April 10, 2020 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

Pembrolizumab Treatment and Pathologic Therapeutic Evaluation for Granulocyte Colony-stimulating Factor-producing Bladder Cancer: A Case Report and Literature Review
We report a case of the pathologically evaluated antitumor effect of pembrolizumab, a programmed death-1 immune checkpoint inhibitor antibody, in G-CSF-producing bladder cancer. A 53-year-old male patient underwent 4 courses chemotherapy with a combination of gemcitabine and carboplatin before a radical cystectomy with ileal neobladder. Four months after the surgery, local recurrence was detected in the pelvis and therefore pembrolizumab was used. One week after its administration, the patient showed increased mucus in his urine. A computed tomography scan and cystoscopy revealed a fistula between the ileum and the neoblad...
Source: Journal of Immunotherapy - April 10, 2020 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

Patched 1-interacting Peptide Represses Fibrosis in Pancreatic Cancer to Augment the Effectiveness of Immunotherapy
We examined the influence of a Hedgehog signal inhibitor, Patched 1-interacting peptide, on fibrosis, infiltration of immune cells, and immunotherapeutic effects on PDAC. We found that this peptide inhibited proliferation and migration of cancer-associated fibroblasts and cancer cells. Furthermore, this peptide reduced the production of extracellular matrix and transforming growth factor β1 in cancer-associated fibroblasts and induced expression of HLA-ABC in PDAC cells and interferon-γ in lymphocytes. In vivo, the peptide suppressed fibrosis of PDAC and increased immune cell infiltration into tumors. The combin...
Source: Journal of Immunotherapy - April 10, 2020 Category: Allergy & Immunology Tags: Basic Studies Source Type: research

Antitumor Potency of an Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy, Lisocabtagene Maraleucel in Combination With Ibrutinib or Acalabrutinib
This study assessed the in vitro and in vivo functionality of CAR T cells transduced to express the anti-CD19 CAR of liso-cel in combination with ibrutinib or acalabrutinib. In prolonged stimulation assays, the presence of ibrutinib or acalabrutinib improved the CAR T-cell effector function. RNA-Seq analysis and surface marker profiling of these CAR T cells treated with ibrutinib but not acalabrutinib revealed gene expression changes consistent with skewing toward a memory-like, type 1 T-helper, Bruton tyrosine kinase phenotype. Ibrutinib or acalabrutinib improved CD19+ tumor clearance and prolonged survival of tumor-beari...
Source: Journal of Immunotherapy - April 10, 2020 Category: Allergy & Immunology Tags: Basic Studies Source Type: research

Brief Communication: Immune Checkpoint Inhibitor-induced Diaphragmatic Dysfunction: A Case Series
Diaphragmatic dysfunction is a rare cause of dyspnea that can lead to hypercapnic respiratory failure. A variety of causes of diaphragmatic dysfunction have been identified, including myopathies and neuropathies, the latter of which can be further subdivided into infectious, idiopathic, demyelinating, malignant, and iatrogenic etiologies. Now, in the era of immune checkpoint inhibitors (ICIs), case reports of immune-mediated phrenic nerve palsies have been described. This diagnosis can be challenging to make, as dyspnea is a common presenting complaint and immune-mediated palsy of the phrenic nerve is a rarely described co...
Source: Journal of Immunotherapy - March 10, 2020 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

The Anticancer Efficacy of Immune Checkpoint Inhibitors According to Patients’ Age: A Systematic Review and Meta-Analysis
Limited prospective data about the activity of immune checkpoint inhibitors (ICIs) are available for elderly patients. The aim of our analysis was to determine the relative efficacy of ICIs versus available standard therapies [standard of care (SOC)] in subgroups defined by patients’ age. Searching the MEDLINE/PubMed, Cochrane Library, and American Society of Clinical Oncology (ASCO) Meeting abstracts randomized clinical trials were identified. Data extraction was conduced according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement. The measured outcome was overall survival (...
Source: Journal of Immunotherapy - March 10, 2020 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

Bilateral Vocal Cord Paralysis Due to an Immune-related Adverse Event of Nivolumab: A Case Report
Summary: Nivolumab is an anti-programmed death-1 inhibitor used in the treatment of cancer. Nivolumab has recently been approved as an adjuvant treatment for patients with stage IIIB, IIIC, and completely resected stage IV melanoma in the Netherlands. Despite the promising results of nivolumab, there is a wide variation in toxic side effects. A nivolumab-induced bilateral vocal cord paralysis (BVCP) was not reported. In this case, we present a nivolumab-induced BVCP. A 75-year-old man received nivolumab as adjuvant therapy for stage III melanoma. After the first cycle of nivolumab, this patient developed immune-related h...
Source: Journal of Immunotherapy - March 10, 2020 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

Combination Therapy of Ipilimumab and Nivolumab-associated Toxic Epidermal Necrolysis (TEN) in a Patient With Metastatic Melanoma: A Case Report and Literature Review
Ipilimumab and nivolumab are immune checkpoint inhibitors used in the treatment of metastatic melanoma. The authors report the case of a 62-year-old white male individual with metastatic choroidal melanoma who had commenced adjuvant systemic treatment with combination checkpoint inhibitor therapy of intravenous ipilimumab (anti-cytotoxic T-lymphocyte antigen-4) and nivolumab (anti-programmed cell death-1) at 3-week cycle intervals. On day 4 after the second cycle, he developed an acute widespread rash. On examination there was confluent erythema with bullae and epidermal loss over 60% of the body surface area, with severe ...
Source: Journal of Immunotherapy - March 10, 2020 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

Generation of Antitumor T Cells For Adoptive Cell Therapy With Artificial Antigen Presenting Cells
Adoptive cell therapy with ex vivo expanded tumor infiltrating lymphocytes or gene engineering T cells expressing chimeric antigen receptors (CAR) is a promising treatment for cancer patients. This production utilizes T-cell activation and transduction with activation beads and RetroNectin, respectively. However, the high cost of production is an obstacle for the broad clinical application of novel immunotherapeutic cell products. To facilitate production we refined our approach by using artificial antigen presenting cells (aAPCs) with receptors that ligate CD3, CD28, and the CD137 ligand (CD137L or 41BBL), as well as expr...
Source: Journal of Immunotherapy - March 10, 2020 Category: Allergy & Immunology Tags: Basic Study Source Type: research

Sarcoid-like Reaction Discovered on EBUS-TBNA of Intrathoracic Lymph Nodes During Immunotherapy for Metastatic Melanoma
The use of immune checkpoint inhibitors has dramatically improved outcomes for patients with advanced melanoma and other malignancies. Checkpoint inhibitors are associated with a unique set of toxicities collectively known as immune-related adverse events, the incidence of which is rising in parallel with their increasing use in clinical practice. Immune-related adverse events are widely variable in their presentation and can affect virtually any organ system in the body. Sarcoid-like reactions in patients being treated with immune checkpoint inhibitors are rare and are typically multisystemic in nature with isolated pulmo...
Source: Journal of Immunotherapy - February 1, 2020 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

Immune-related Neutropenia Following Treatment With Immune Checkpoint Inhibitors
The existing data with regard to immune-related neutropenia (irN), a rare (incidence—1%) immune-related adverse event of immune checkpoint inhibitors, are scarce. Eight patients with irN were identified through internal databases of 3 participating Israeli cancer centers. In addition, 11 original articles focusing on the clinical course of 24 patients with irN were selected during the PubMed search. Descriptive analysis of clinical and pathologic factors related to irN was performed (n=32); the effect of these on the irN outcomes was assessed. An algorithm for irN evaluation and treatment was proposed. The median tim...
Source: Journal of Immunotherapy - February 1, 2020 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

Blood Immune Cell Biomarkers in Patient With Lung Cancer Undergoing Treatment With Checkpoint Blockade
Characterization of host immune cell parameters before and during immunotherapy is expected to identify predictive biomarkers for clinical outcome. We prospectively monitored blood immune cells from 35 patients with advanced non–small cell lung cancer undergoing checkpoint inhibitor monotherapy. The aim was to identify parameters correlating with better/worse outcome. Peripheral blood was serially collected before each infusion at the onset and at cycle 3 and 5 of immunotherapy. A complete leukocyte blood count, the lymphocytic subpopulations and the percentages of both HLA-DRlow monocytes and dendritic cells (DC) we...
Source: Journal of Immunotherapy - February 1, 2020 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

Applicability of Routine Targeted Next-generation Sequencing to Estimate Tumor Mutational Burden (TMB) in Patients Treated With Immune Checkpoint Inhibitor Therapy
It remains unclear whether targeted next-generation sequencing (tNGS) conveys a reliable estimate of tumor mutational burden (TMB). We sequenced 79 archival samples of immune checkpoint inhibitors (ICPIs) recipients (57% lung cancer, 43% melanoma) using Ion Ampliseq Cancer Hotspot Panel. Employing multiple cutoff values, we verified that TMB by tNGS did not correlate with response or survival following ICPI. We found enrichment of ATM mutations in ICPI-refractory tumors (P=0.01) to correlate with worse survival (4.2 vs. 10 mo, P=0.03). Limited-coverage tNGS delivers an imprecise estimate of patients’ TMB but m...
Source: Journal of Immunotherapy - February 1, 2020 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

An IgG1 Version of the Anti-transferrin Receptor 1 Antibody ch128.1 Shows Significant Antitumor Activity Against Different Xenograft Models of Multiple Myeloma: A Brief Communication
The transferrin receptor 1 (TfR1) is a meaningful target for antibody-based cancer therapy given its overexpression on malignant cells and its central role in cancer pathology. We previously developed a mouse/human chimeric IgG3 targeting human TfR1 (ch128.1), which exhibits significant antitumor activity against multiple myeloma (MM) in xenograft models of SCID-Beige mice bearing disseminated ARH-77 or KMS-11 tumors. This activity is observed in early and late disease stages of disseminated KMS-11 tumors and, in this model, the mechanism of antitumor activity is Fc-mediated, involving macrophages. As human IgG1 is the iso...
Source: Journal of Immunotherapy - February 1, 2020 Category: Allergy & Immunology Tags: Basic Studies Source Type: research

Identification of Different Form Tim-3 Proteins by a Unique Set of Tim-3 Monoclonal Antibodies
In this study, we have successfully developed a unique set of Tim-3 antibodies that are able to detect different molecular weights (by Western blot mobility) of Tim-3 proteins ectopically expressed in the same CHO cells. Some of the antibody clones detect only 33 or 55 kDa bands, the rest can recognize both 33 and 55 kDa bands on polyacrylamide gel electrophoresis gel. Antibody clones with 55 kDa specificity uniquely bind to the membrane form of Tim-3 on macrophage, which colocalizes with the CD68, and could be used as a specific marker for tumor-associated macrophage, whereas other clones showed cytop...
Source: Journal of Immunotherapy - February 1, 2020 Category: Allergy & Immunology Tags: Basic Studies Source Type: research

Nivolumab-induced Adrenal Insufficiency in Patients With Renal Cell Carcinoma
In conclusion, we described, for the first time, a case series of nivolumab-induced adrenal insufficiency in patients with mRCC. Our findings may be useful for the accurate diagnosis and the prompt treatment of this condition. In addition, there is a possibility that adrenal insufficiency may be associated with a favorable response to nivolumab in patients with mRCC. (Source: Journal of Immunotherapy)
Source: Journal of Immunotherapy - December 9, 2019 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

Radiation Priming Chimeric Antigen Receptor T-Cell Therapy in Relapsed/Refractory Diffuse Large B-Cell Lymphoma With High Tumor Burden
This study demonstrates that radiotherapy is an optimal debulking regimen to managing R/R DLBCL patients before CAR-T therapy and a promising alternative salvage therapy for patients who suffer a relapse after CAR-T therapy by fuelling CAR-T copies. (Source: Journal of Immunotherapy)
Source: Journal of Immunotherapy - December 9, 2019 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

Severe Acute Kidney Injury Due to Nivolumab/Ipilimumab-induced Granulomatosis and Fibrinoid Vascular Necrosis
Immune-checkpoint inhibitors have revolutionized the treatment of cancers in recent years. Four drugs have obtained FDA approval in a variety of cancer types. Immune-related adverse events are common and occur in up to 60% of treated patients. Common manifestations of immune-related adverse events include rash, colitis, hepatitis, and hypophysitis. Most cases are mild to moderate in grade; however, severe manifestations with lethal outcomes have been described. Acute kidney injury is reported as a rare complication. In this case report, we present a patient with metastatic melanoma undergoing combined immune-checkpoint inh...
Source: Journal of Immunotherapy - December 9, 2019 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

CAIX-specific CAR-T Cells and Sunitinib Show Synergistic Effects Against Metastatic Renal Cancer Models
Treatment with chimeric antigen receptor-modified T cell (CAR-T) has demonstrated promising therapeutic efficacy in hematologic malignancies. However, the therapeutic efficacy is still very limited for solid tumors. An immunosuppressive microenvironment is one of the main reasons for the limited efficacy. Some chemotherapeutic agents exhibit immune microenvironment modulation. Therefore, combination with chemotherapeutic agents may be one of the promising strategies to enhance the therapeutic efficacy of CAR-T against solid tumors. Sunitinib modulates the antitumor immune response by improving T-cell infiltration and funct...
Source: Journal of Immunotherapy - December 9, 2019 Category: Allergy & Immunology Tags: Basic Study Source Type: research

Association of Insurance Status With Presentation, Treatment, and Survival in Melanoma in the Era of Immune Checkpoint Inhibitors
The effect of health insurance on management and outcomes in melanoma is unclear. Using the National Cancer Database (NCDB), we evaluated the effect of insurance on (1) stage at diagnosis, (2) receipt of immunotherapy, and (3) overall survival (OS) among patients with melanoma. We included patients with stage I–IV melanoma diagnosed from 2011 to 2015. Patients were stratified by age (below 65 vs. 65 y or above) and insurance (commercial, Medicare, Medicaid and uninsured). We evaluated the association between insurance and (1) stage at diagnosis (stage I–III vs. IV) and (2) receipt of immunotherapy (stage...
Source: Journal of Immunotherapy - December 9, 2019 Category: Allergy & Immunology Tags: Review Articles Source Type: research

Immune-related Adverse Events and Survival in Solid Tumors Treated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis
Immune-related adverse events (irAEs) are autoimmune-toxic effects associated with immune checkpoint inhibitors (ICIs) used for the treatment of advanced solid tumors. We performed a systematic review and meta-analysis of the published literature to assess the outcome for cancer patients treated with ICIs who develop irAEs. Two independent reviewers selected prospective or retrospective studies from PubMed, EMBASE, and the Cochrane Library database from their inception to November 2018. Data were pooled using hazard ratios (HRs) for overall survival or progression-free survival or odds ratio for overall response rate of ir...
Source: Journal of Immunotherapy - December 9, 2019 Category: Allergy & Immunology Tags: Review Articles Source Type: research

A Severe, Refractory Case of Mucous Membrane Pemphigoid After Treatment With Pembrolizumab: Brief Communication
Pembrolizumab is a humanized antibody that targets the programmed death-1 receptor expressed in T cells with high selectivity. This therapeutic is of great importance in cancer immunotherapy yet managing the potential immune-related adverse events remains a concern. Here, we report a rare case of mucous membrane pemphigoid in the oral mucosa, upper respiratory tract, and conjunctiva of a patient with ovarian adenocarcinoma without cutaneous manifestation, which persisted even after pembrolizumab discontinuation. A brief review of pembrolizumab-related bullous pemphigoid cases is presented and possible mechanisms underlying...
Source: Journal of Immunotherapy - October 10, 2019 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

Immunogenomic Analysis of Exceptional Responder to ALT-803 (IL-15 Analogue) in BCG Unresponsive Nonmuscle Invasive Bladder Cancer: A Case Series and Review of the Literature
The clinical validity and utility of complex biomarkers have not been extensively studied in bladder cancer. Three patients with nonmuscle invasive bladder cancer [1 patient with an exceptional response; complete response (CR) for 30 months] who failed intravesical BCG were evaluated using an NYS CLEP approved assay, Immune Report Card, which measures programmed death-ligand 1 expression, CD8+ T-cell infiltration pattern, mutational burden, and gene expression of 51 immune-related transcripts using RNA-Seq. Patients were tested before being treated under our expanded access protocol for intravesical BCG with ALT-803. Subje...
Source: Journal of Immunotherapy - October 10, 2019 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

Superimposed Clostridium difficile Infection During Checkpoint Inhibitor Immunotherapy-induced Colitis
This report described the course of the 2 medical conditions in these patients. On the basis of our experiences, CDI may occur as a superimposed infection during ICI-induced colitis. Although ICI-induced colitis may be a risk factor for CDI, the observed association may be fortuitous. Future study will be needed to characterize the association between CDI and ICI-induced colitis. Clinicians should be mindful of possible co-occurrence of both conditions to promptly and adequately institute effective interventions. (Source: Journal of Immunotherapy)
Source: Journal of Immunotherapy - October 10, 2019 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

Nivolumab and Ipilimumab-induced Acute Inflammatory Demyelinating Polyradiculoneuropathy: A Case Report
Immunotherapies such as the cytotoxic T-lymphocyte–associated protein 4 inhibitor ipilimumab and the programmed cell death protein 1 inhibitor nivolumab have become ubiquitous in cancer treatment. Recently, the FDA approved nivolumab with or without ipilimumab for the treatment of refractory small cell lung cancer. Immunotherapies increase the immune response to cancer cells by interfering with inhibitory molecular pathways that prevent tumor cell killing, thus augmenting tumor cell death without many of the cytotoxic side effects associated with chemotherapy. However, this augmented immune response may result in unw...
Source: Journal of Immunotherapy - October 10, 2019 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

Linear IgA Disease of the Gingiva Following Nivolumab Therapy
We report the first case of gingival linear immunoglobulin A disease related to treatment with an antiprogrammed cell death protein 1 antibody. A 73-year-old male with advanced non–small cell lung cancer achieved a durable response to nivolumab monotherapy. After 1 year of treatment, he developed gingival swelling and pain. Biopsy revealed linear immunoglobulin A disease of the gingiva which was effectively treated with systemic steroids. Ongoing vigilance for immune-mediated toxicity is paramount during and after treatment with immune checkpoint inhibitors. (Source: Journal of Immunotherapy)
Source: Journal of Immunotherapy - October 10, 2019 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

Improving Immunotherapy Against B-Cell Malignancies Using γδ T-Cell–specific Stimulation and Therapeutic Monoclonal Antibodies
This study expands on earlier reports on the therapeutic potential of distinctive tumor antigen–targeting mAbs and facilitates the understanding of the mechanism and potential of ADCC by γδ T-cell subsets. (Source: Journal of Immunotherapy)
Source: Journal of Immunotherapy - October 10, 2019 Category: Allergy & Immunology Tags: Basic Studies Source Type: research

Checkpoint Blockade in Combination With Doxorubicin Augments Tumor Cell Apoptosis in Osteosarcoma
The aim of this study was to provide a basis for the theory that the combination of conventional chemotherapy and immunotherapy would be an effective treatment for osteosarcoma. Here, the expression of programmed death ligand 1 (PD-L1) in 26 clinical osteosarcoma tissue samples collected before and after chemotherapy was analyzed. The effects of osteosarcoma cells treated with doxorubicin, a conventional chemotherapeutic agent, on the proliferation and apoptosis of CD8+ T lymphocytes were investigated in vitro. Thereafter, the effectiveness of doxorubicin combined with an anti-PD-L1 antibody as an osteosarcoma therapy was ...
Source: Journal of Immunotherapy - October 10, 2019 Category: Allergy & Immunology Tags: Basic Studies Source Type: research

Autoimmune Bell’s Palsy Following Immunotherapy For Metastatic Melanoma: A Report of 2 Cases
We describe 2 cases of autoimmune Bell’s palsy following the administration of combination ICT using ipilimumab and nivolumab in 2 patients with metastatic melanoma. The use of a steroid taper in addition to the cessation of combination immunotherapy resulted in resolution of symptoms for both patients. In the first case, the patient was subsequently started on nivolumab monotherapy but developed autoimmune polyneuropathy, and immunotherapy was discontinued indefinitely. In the second case, the initiation of nivolumab monotherapy following resolution of symptoms resulted in an inadequate antitumoral response. Subsequ...
Source: Journal of Immunotherapy - September 7, 2019 Category: Allergy & Immunology Tags: Clincal Studies Source Type: research