Clinical translation and regulatory aspects of CAR/TCR-based adoptive cell therapies —the German Cancer Consortium approach

AbstractAdoptive transfer of T cells genetically modified by TCRs or CARs represents a highly attractive novel therapeutic strategy to treat malignant diseases. Various approaches for the development of such gene therapy medicinal products (GTMPs) have been initiated by scientists in recent years. To date, however, the number of clinical trials commenced in Germany and Europe is still low. Several hurdles may contribute to the delay in clinical translation of these therapeutic innovations including the significant complexity of manufacture and non-clinical testing of these novel medicinal products, the limited knowledge about the intricate regulatory requirements of the academic developers as well as limitations of funds for clinical testing. A suitable good manufacturing practice (GMP) environment is a key prerequisite and platform for the development, validation, and manufacture of such cell-based therapies, but may also represent a bottleneck for clinical translation. The German Cancer Consortium (DKTK) and the Paul-Ehrlich-Institut (PEI) have initiated joint efforts of researchers and regulators to facilitate and advance early phase, academia-driven clinical trials. Starting with a workshop held in 2016, stakeholders from academia and regulatory authorities in Germany have entered into continuing discussions on a diversity of scientific, manufacturing, and regulatory aspects, as well as the benefits and risks of clinical application of CAR/TCR-based cell therapies. This r...
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research

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Authors: Mkango SB, Shaban N, Mureithi E, Ngoma T Abstract A type of cancer which originates from the breast tissue is referred to as breast cancer. Globally, it is the most common cause of death in women. Treatments such as radiotherapy, chemotherapy, hormone therapy, immunotherapy, and gene therapy are the main strategies in the fight against breast cancer. The present study aims at investigating the effects of the combined radiotherapy and chemotherapy as a way to treat breast cancer, and different treatment approaches are incorporated into the model. Also, the model is fitted to data on patients with breast can...
Source: Computational and Mathematical Methods in Medicine - Category: Statistics Tags: Comput Math Methods Med Source Type: research
In conclusion, a polypharmacology approach of combining established, prolongevity drug inhibitors of specific nodes may be the most effective way to target the nutrient-sensing network to improve late-life health. Deletion of p38α in Neurons Slows Neural Stem Cell Decline and Loss of Cognitive Function in Mice https://www.fightaging.org/archives/2019/10/deletion-of-p38%ce%b1-in-neurons-slows-neural-stem-cell-decline-and-loss-of-cognitive-function-in-mice/ Researchers here provide evidence for p38α to be involved in the regulation of diminished neural stem cell activity with age. It is thought...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
In conclusion, our findings link the calcification of the vascular tissue with the expression of FGF23 in the vessels and with the elevation of circulating levels this hormone. Permanently Boosting Levels of Natural Killer Cells in Mice to Increase Cancer Resistance https://www.fightaging.org/archives/2019/09/permanently-boosting-levels-of-natural-killer-cells-in-mice-to-increase-cancer-resistance/ Researchers here demonstrate a very interesting approach to immunotherapy: they introduce engineered stem cells in mice that will give rise to additional natural killer T cells, boosting the capability of the ...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
A promising and expensive type of immunotherapy, called CAR T-cell therapy, is now covered by Medicare. This news may affect mesothelioma patients in the future. Chimeric antigen receptor T-cell, or CAR T-cell, therapy involves the laboratory reprogramming of a patient’s T cells, which are a type of white blood cell responsible for protecting the body against infection and disease. The T cells are genetically modified to better recognize and attack cancer. The U.S. Food and Drug Administration has approved the immunotherapy procedure for non-Hodgkin lymphoma and B-cell precursor acute lymphoblastic leukemia. It is...
Source: Asbestos and Mesothelioma News - Category: Environmental Health Authors: Source Type: news
Pioneering pulmonologists Dr. Steven Albelda and Dr. Daniel Sterman have worked for more than 20 years on developing gene therapy to effectively combat pleural mesothelioma cancer. The payoff may have finally arrived. Albelda and Sterman’s long-awaited, phase III clinical trial will open this month to evaluate the efficacy of TR002, a novel gene therapy drug, when used in combination with celecoxib and gemcitabine. TR002, a form of immunotherapy, is a genetically engineered adenovirus that triggers the anti-tumor effects of interferon, a naturally occurring protein that destroys cancer cells. “The hope is, if i...
Source: Asbestos and Mesothelioma News - Category: Environmental Health Authors: Source Type: news
In conclusion, our data show how oncogenic and tumor-suppressive drivers of cellular senescence act to regulate surveillance processes that can be circumvented to enable SnCs to elude immune recognition but can be reversed by cell surface-targeted interventions to purge the SnCs that persist in vitro and in patients. Since eliminating SnCs can prevent tumor progression, delay the onset of degenerative diseases, and restore fitness; since NKG2D-Ls are not widely expressed in healthy human tissues and NKG2D-L shedding is an evasion mechanism also employed by tumor cells; and since increasing numbers of B cells express NKG2D ...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Authors: Tse J, Singla N, Ghandour R, Lotan Y, Margulis V Abstract Introduction: The current first line therapy for high grade (HG) non-muscle invasive bladder cancer (NMIBC) is intravesical Bacillus Calmette-Guerin (BCG). Patients who recur or progress despite BCG are recommended to undergo radical cystectomy or participate in clinical trials. There is an urgent need for alternative therapies in the BCG-unresponsive NMIBC realm. Areas covered: We queried clinicaltrials.gov and pubmed.gov for current and recently completed early clinical trials pertaining to investigational agents used for the treatment of BCG-unre...
Source: Expert Opinion on Investigational Drugs - Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research
Adam Ford of Science, Technology, and the Future carried out a number of interviews while at Undoing Aging in Berlin earlier this year. The interview materials are steadily being processed and uploaded, and that just recently included this interview with Jim Mellon, billionaire investor and philanthropist, cofounder of Juvenescence, and a very down to earth fellow who is interested in improving the human condition by targeting aging with new biotechnologies. Accordingly, he has used his resources to put himself into a position to talk up the longevity industry, move research forward, and attract a great deal more funding f...
Source: Fight Aging! - Category: Research Authors: Tags: Healthy Life Extension Community Source Type: blogs
Cancer Gene Therapy, Published online: 06 August 2019; doi:10.1038/s41417-019-0126-6Cancer immunotherapy using the Fusion gene of Sendai virus
Source: Cancer Gene Therapy - Category: Cancer & Oncology Authors: Source Type: research
This article introduces the main concepts and addresses the most relevant clinical modalities of cellular immunotherapies for hematological malignancies: antigen non-specific T cell therapy, genetically modified T cell receptor (TCR) T cell therapy, chimeric antigen receptor (CAR) T cell therapy, and CAR-T cell clinical trials in leukemia, lymphoma, and multiple myeloma. Clinical trials have shown encouraging results, but future studies may need to incorporate novel CAR constructs or targets with enhanced safety and efficacy to ensure long-term benefits. PMID: 31338822 [PubMed - in process]
Source: Advances in Experimental Medicine and Biology - Category: Research Tags: Adv Exp Med Biol Source Type: research
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