Cancers, Vol. 12, Pages 915: Fully Human Antibodies for Malignant Pleural Mesothelioma Targeting

Cancers, Vol. 12, Pages 915: Fully Human Antibodies for Malignant Pleural Mesothelioma Targeting Cancers doi: 10.3390/cancers12040915 Authors: Nicolini Bocchini Angeli Bronte Delmonte Crinò Mazza Immunotherapy is the most promising therapeutic approach against malignant pleural mesothelioma (MPM). Despite technological progress, the number of targetable antigens or specific antibodies is limited, thus hindering the full potential of recent therapeutic interventions. All possibilities of finding new targeting molecules must be exploited. The specificity of targeting is guaranteed by the use of monoclonal antibodies, while fully human antibodies are preferred, as they are functional and generate no neutralizing antibodies. The aim of this review is to appraise the latest advances in screening methods dedicated to the identification and harnessing of fully human antibodies. The scope of identifying useful molecules proceeds along two avenues, i.e., through the antigen-first or binding-first approaches. The first relies on screening human antibody libraries or plasma from immunized transgenic mice or humans to isolate binders to specific antigens. The latter takes advantage of specific binding to tumor cells of antibodies present in phage display libraries or in responders’ plasma samples without prior knowledge of the antigens. Additionally, next-generation sequencing analysis of B-cell receptor repertoire pre- and post-therapy in memo...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research

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Malignant pleural mesothelioma (MPM) is a treatment recalcitrant tumor with a poor overall survival (OS). Current approved treatment consists of first line chemotherapy that only modestly increases OS, illustrating the desperate need for other treatment options in MPM. Unfortunately, clinical studies that investigate the effectivity of checkpoint inhibitor (CI) treatment failed to improve clinical outcome over current applied therapies. In general, MPM is characterized as an immunological cold tumor with low T-cell infiltration, which could explain the disappointing results of clinical trials investigating CI treatment in ...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
An international, much-anticipated phase III clinical trial that could change standard-of-care treatment for patients with malignant pleural mesothelioma will open soon, pending COVID-19 pandemic restrictions. The randomized trial will be studying the effectiveness of the immunotherapy drug durvalumab (Imfinzi) when used in combination with chemotherapy drugs pemetrexed (Alimta) and cisplatin for mesothelioma. Opening dates may vary by center because of the COVID-19 pandemic that has slowed or stalled clinical trials everywhere. Durvalumab produces an antibody that helps a patient’s own immune system kill tumor cell...
Source: Asbestos and Mesothelioma News - Category: Environmental Health Authors: Source Type: news
Conclusions: Since its introduction, PERCIST 1.0 has been increasingly used in many clinical trials and prospective studies, with variable reporting of metabolic response and survival data. In general, it appears PERCIST response is associated with longer PFS and survival though the heterogeneity of disease, scan timing and therapies make data pooling difficult. Prospective inclusion of the PERCIST 1.0 criteria in clinical trials using FDG, with baseline, early monitoring, and end of therapy scans could inform cancer clinical trials. Support: 5U01CA140204-04 Reference: 1. Wahl RL, Jacene H, Kasamon Y, Lodge MA. From RECIST...
Source: Journal of Nuclear Medicine - Category: Nuclear Medicine Authors: Tags: NET and Others II Source Type: research
This study is open also to patients with lung cancer or urothelial cancer. In the trial, the use of cabozantinib will be combined with standard-of-care Alimta, the chemotherapy drug generically known as pemetrexed. The study is designed to establish a safe and effective dosage level for both agents when used together. Cabozantinib is known as an inhibitor. It blocks signals that encourage the growth of new blood vessels needed for cancer cells to divide and grow. Blocking those signals can shrink tumors or even cause tumor cell death, leading to significantly longer survival for patients. Cabozantinib will be taken orall...
Source: Asbestos and Mesothelioma News - Category: Environmental Health Authors: Source Type: news
Pharmaceutical giant Bristol Myers Squibb continues to tout its immunotherapy combination of Opdivo and Yervoy for first-line treatment of patients with pleural mesothelioma cancer. Bristol Myers Squibb recently announced that overall survival “significantly improved” when the combination was measured against standard chemotherapy in a randomized, phase III clinical trial of previously untreated mesothelioma patients. Its announcement was based on a pre-specific interim analysis conducted by the Data Monitoring Committee, a clinical study organization independent of Bristol Myers Squibb. The study is being cond...
Source: Asbestos and Mesothelioma News - Category: Environmental Health Authors: Source Type: news
Medical centers across the country have slowed or stopped the enrollment of new patients in mesothelioma clinical trials because of the all-consuming COVID-19 pandemic. The pause in enrollment options could be critical for newly diagnosed patients with pleural mesothelioma, whose life expectancy is often just six to 12 months. Clinical trials are research studies where patients can find cutting-edge treatments not yet approved by the U.S. Food and Drug Administration. Those experimental treatments go beyond standard of care, which generally has not been effective for this rare and aggressive cancer caused by asbestos expos...
Source: Asbestos and Mesothelioma News - Category: Environmental Health Authors: Source Type: news
As the U.S. comes to grips with the challenges of the COVID-19 pandemic, mesothelioma cancer survivors face additional hurdles, including difficulty receiving care. Patients currently undergoing treatment for cancer and those who are immunocompromised are at greater risk of serious health issues if they contract COVID-19, according to the Centers for Disease Control and Prevention. “Cancer patients are a high-risk group and should be extra vigilant in terms of isolation precautions. They should follow the medical authorities’ instructions,” Dr. Ory Wiesel, a thoracic surgeon at Maimonides Medical Center ...
Source: Asbestos and Mesothelioma News - Category: Environmental Health Authors: Source Type: news
Malignant mesothelioma (MM), especially its more frequent form, malignant pleural mesothelioma (MPM), is a devastating thoracic cancer with limited therapeutic options. Recently, clinical trials that used immunotherapy strategies have yielded promising results, but the benefits are restricted to a limited number of patients. To develop new therapeutic strategies and define predictors of treatment response to existing therapy, better knowledge of the cellular and molecular mechanisms of MM tumors and sound preclinical models are needed. This review aims to provide an overview of our present knowledge and issues on both subj...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
A new clinical trial is testing an innovative approach to immunotherapy that could change the way antibodies target pleural mesothelioma tumors. Researchers at eight cancer centers across the U.S. are examining the safety and efficacy of INBRX-109, a unique antibody structure developed to bind with and destroy mesothelioma tumor cells without harming healthy tissue. Enrollment for mesothelioma patients is ongoing for the second stage of the first-in-humans trial. Safety and efficacy reports are expected in the second quarter of 2020. The first stage of the trial reached its endpoint with no reports of toxicity or intoleran...
Source: Asbestos and Mesothelioma News - Category: Environmental Health Authors: Source Type: news
In this study, we took advantage of photodynamic therapy (PDT) to induce immunogenic cell death to generate mesothelioma cell lysates for DC priming and evaluated such a vaccine to treat peritoneal mesothelioma. We found that the white light in vitro activation of the photosensitizer OR141 led to mesothelioma cell death, together with the release of bona fide danger signals that promote DC maturation. The administration of a PDT-based DC vaccine to mice bearing peritoneal mesothelioma led to highly significant survival when compared with sham or control animals treated with anti-CTLA4 antibodies. This was further supported...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
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