Immunotherapy

Our medical research library holds 7 studies published in Immunotherapy (2012–2018). Each entry links to the study's record on PubMed and, where there is one, to the publisher's page and a free full text. 5 have an abstract, the authors' own summary as PubMed records it: open "Abstract" to read it. For 2 studies PubMed has no abstract for, we give the abstract printed in the article or, where there is none, a summary we wrote from it, each labeled as such.

About the journal

• Publisher: Taylor & Francis
• Published: 2009 to the present, England
• Language: English
• ISSN: 1750-743X (print), 1750-7448 (electronic)
• Its record in the NLM Catalog

2010s

• Immunotherapy in relapsed mesothelioma. S. Brosseau, X. Dhalluin, G. Zalcman, et al. 2018;10(2):77-80. Editorial PubMed · Publisher

  Summary

  In this editorial, the authors reviewed immunotherapy, particularly immune checkpoint inhibitors (ICI), as treatment for malignant pleural mesothelioma (MPM) that had relapsed after first-line chemotherapy. They noted that MPM arises mainly after occupational asbestos exposure, that its prognosis remains poor, and that no second-line treatment had been approved. They summarized published and conference-reported trials. Early studies of the anti-PD-1 antibodies pembrolizumab and nivolumab and the anti-PD-L1 antibody avelumab reported disease control rates of 50% to 80%. In contrast, the anti-CTLA-4 antibody tremelimumab did not significantly improve outcome over placebo in the DETERMINE trial of 571 patients (median overall survival 7.7 versus 7.3 months). In the French Phase II MAPS-2 trial, disease control at 12 weeks was 50.0% with nivolumab plus ipilimumab and 44.4% with nivolumab alone. Three treatment-related deaths occurred in the combination arm. A Swiss registry of 48 patients given pembrolizumab reported an objective response rate of 25%, with better results in patients whose tumors expressed PD-L1. The authors concluded that these studies, totalling more than 250 patients, showed significant activity of ICI with acceptable toxicity. They discussed ongoing Phase III trials and possible ethical issues with placebo arms. They also noted that no ideal biomarker yet identified the patients most likely to benefit.

  PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.

• Malignant mesothelioma clinical trial combines immunotherapy drugs. M.S. Chatwal, T. Tanvetyanon. 2018;10(5):341-344. Editorial PubMed · Publisher

  Abstract

  Immunotherapy by checkpoint inhibitor is effective for a number of solid tumors including malignant mesothelioma. Studies utilizing single-agent PD-1 or PD-L1 inhibitor for mesothelioma have reported tumor response rates in approximately 10-20% of patients treated. Given the success of combining these agents with CTLA-4 inhibitor in melanoma, there is a strong rationale to study it in mesothelioma. Recently results from clinical trials investigating this approach have been released. Though limited by small sample size, the studies conclusively demonstrated feasibility and suggested a modestly higher tumor response rate than one would expect from treatment with single-agent PD-1 or PD-L1 inhibitor. Nevertheless, toxicity was also increased. Immunotherapy-related deaths due to encephalitis, renal failure and hepatitis were observed. Further studies are warranted.

• Anti-CTLA-4 therapy for malignant mesothelioma. A. Guazzelli, E. Bakker, M. Krstic-Demonacos, et al. 2017;9(3):273-280. Review PubMed · Publisher

  Abstract

  Immunotherapy is an emerging therapeutic strategy with a promising clinical outcome in some solid tumors, particularly metastatic melanoma. One approach to immunotherapy is immune checkpoint inhibitors, such as blockage of CTLA-4 and PD-1/PD-L1. This special report aims to describe the state of clinical trials of tremelimumab in patients with unresectable malignant mesothelioma (MM) in particular with regard to the clinical efficacy, safety and tolerability. Criticism and perspective of this treatment are also discussed. Biological and clinical considerations rule out the use of tremelimumab as single agent for MM and, more generally, the use of immune checkpoint inhibitors for MM is still largely questionable and not supported by evidences.

• Overcoming barriers of car T-cell therapy in patients with mesothelin-expressing cancers. M.H. O'Hara, C. Stashwick, G. Plesa, et al. 2017;9(9):767-780. Review PubMed · Publisher

  Abstract

  One obstacle to the application of immunotherapy to solid malignancies is to overcome the existing tolerance to self-antigens. Vaccine strategies aimed at harnessing endogenous antitumor T cells are limited by the T-cell receptor repertoire, which can be detected within the thymus as central tolerance or rendered nonfunctional by post-thymic mechanisms of peripheral tolerance. Adoptive immunotherapy can overcome these obstacles, since therapeutically effective T cells can be engineered to recognize tumors. Continued advancements in novel treatments, including immunotherapy, in solid malignancies are imperative. While mesothelin is an attractive target for cancer immunotherapy given its normal expression is limited to mesothelial cells, the breakthrough for chimeric antigen receptor T-cell treatment against this antigen is still forthcoming.

• A regional approach for CAR T-cell therapy for mesothelioma: from mouse models to clinical trial. M. Mayor, M. Zeltsman, E. McGee, et al. 2016;8(5):491-4. Editorial PubMed · Publisher

  Summary

  In this editorial, researchers from Memorial Sloan Kettering Cancer Center discussed regional (intrapleural) delivery of chimeric antigen receptor (CAR) T-cell therapy for malignant pleural mesothelioma (MPM). They described MPM as a rare, highly aggressive pleural tumor with a median survival of 9–20 months, whose harm results mainly from local invasion rather than distant spread. Earlier intrapleural treatments, including chemotherapy, photodynamic therapy, brachytherapy, oncolytic viruses, IFN-β gene transfer and IL-2, had limited success. The authors summarized their earlier studies of 175 and 230 patients with epithelioid MPM, which linked immune features of the tumor to survival. They presented mesothelin as a target antigen and noted that a Phase II trial of amatuximab with pemetrexed and cisplatin reported a 40% partial response rate and a 51% stable disease rate. In their orthotopic mouse model, mesothelin-targeted CAR T cells given intrapleurally eradicated established pleural tumors at a 30-fold lower dose than cells given intravenously. CD4+ CAR T cells were important to this effect and gave protection against tumor challenge at 196 days. In an earlier intravenous Phase I trial that included three MPM patients, all three developed antibodies and one had an anaphylactic reaction. The authors described their ongoing Phase I trial (NCT02414269), which gives the cells through an indwelling intrapleural catheter. They concluded that regional CAR T-cell delivery deserves investigation for locoregionally aggressive solid tumors.

  PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.

• Mesothelin as a target for chimeric antigen receptor-modified T cells as anticancer therapy. M. O'Hara, C. Stashwick, A.R. Haas, et al. 2016;8(4):449-60. Review PubMed · Publisher · Free full text

  Abstract

  Mesothelin is a promising target for immune-based therapy, specifically for mesothelioma and pancreatic and ovarian cancers that have high levels of mesothelin expression. Many preclinical and clinical studies that target tumors with high mesothelin expression with antibodies, immunotoxins, antibody-drug conjugates and vaccines have shown the potential of mesothelin as a target. Studies of T cells genetically modified with chimeric antigen receptors (CAR) report significant efficacy in hematologic malignancies, and antimesothelin CAR T cells are currently being investigated in clinical studies. Here we outline the rationale for using mesothelin as a target for immunotherapy, review the clinical and preclinical studies evaluating mesothelin-directed therapies and explore the promise of CAR T cells directed against mesothelin for immunotherapy in the future.

• Dendritic cell-based immunotherapy in mesothelioma. R. Cornelissen, L.A. Lievense, M.E. Heuvers, et al. 2012;4(10):1011-22. Review PubMed · Publisher

  Abstract

  Mesothelioma is a rare thoracic malignancy with a dismal prognosis. Current treatment options are scarce and clinical outcomes are rather disappointing. Due to the immunogenic nature of mesothelioma, several studies have investigated immunotherapeutic strategies to improve the prognosis of patients with mesothelioma. In the last decade, progress in knowledge of the modulation of the immune system to attack the tumor has been remarkable, but the optimal strategy for immunotherapy has yet to be unraveled. Because of their potent antigen-presenting capacity, dendritic cells are acknowledged as a promising agent in immunotherapeutic approaches in a number of malignancies. This review gives an update and provides a future perspective in which immunotherapy may improve the outcome of mesothelioma therapy.

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