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 randomiz...
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
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 of the injectio...
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 differentiation. Blocking STAT5 or n...
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
