T–Cell Engineering for Chimeric Antigen Receptor T–Cell Therapy in Cancer

Through T-cell engineering, researchers at the California South University (CSU) Cancer Research Institute (CRI) have shown that tumor growth can be stopped in a variety of cancers and prevented from spreading to other tissues. Findings from this study are the result of decades of research by Professor Alireza Haidari, a member of the Cancer Biology Research Program at the California South University (CSU), who discovered a protein called AH that can inhibit the growth and spread of cancer cells in several different ways. They become in the tissues of the body. Keywords: Cancer; Cells; Tissues; Tumors; Prevention; Prognosis; Diagnosis; Imaging; Screening, Treatment; Management

Using chimeric antigen receptor T-cell therapy to fight glioblastoma multiforme: past, present and future developments

Introduction Glioblastoma multiforme (GBM) constitutes one of the deadliest tumors to afflict humans, although it is still considered an orphan disease. Despite testing multiple new and innovative therapies in ongoing clinical trials, the median survival for this type of malignancy is less than two years after initial diagnosis, regardless of therapy. One class of promising new therapies are chimeric antigen receptor T cells or CAR-T which have been shown to be very effective at treating refractory liquid tumors such as B-cell malignancies. However, CAR-T effectivity against solid tumors such as GBM has been limited thus far. Methods A Pubmed, Google Scholar, Directory of Open Access Journals, and Web of Science literature search using the terms chimeric antigen receptor or CAR-T, GBM, solid tumor immunotherapy, immunotherapy, and CAR-T combination was performed for publication dates between January 1987 and November 2021. Results In the current review, we present a comprehensive list of CAR-T cells developed to treat GBM, we describe new possible T-cell engineering strategies against GBM while presenting a short introductory history to the reader regarding the origin(s) of this cutting-edge therapy. We have also compiled a unique list of anti-GBM CAR-Ts with their specific protein sequences and their functions as well as an inventory of clinical trials involving CAR-T and GBM. Conclusions The aim of this review is to introduce the reader to the field of T-cell engineering using CAR-Ts to treat GBM and describe the obstacles that may need to be addressed in order to significantly delay the relentless growth of GBM.

T Cell Engineering as Therapy for Cancer and HIV

Through T-cell engineering, researchers at the California South University (CSU) Cancer Research Institute (CRI) have shown that tumor growth can be stopped in a variety of cancers and prevented from spreading to other tissues. Findings from this study are the result of decades of research by Professor Alireza Heidari, a member of the Cancer Biology Research Program at the California South University (CSU), who discovered a protein called AH that can inhibit the growth and spread of cancer cells in several different ways. They become in the tissues of the body. Keywords: Cancer; Cells; Tissues, Tumors; Prevention, Prognosis; Diagnosis; Imaging; Screening; Treatment; Management

γδ T Cells for Leukemia Immunotherapy: New and Expanding Trends

Recently, many discoveries have elucidated the cellular and molecular diversity in the leukemic microenvironment and improved our knowledge regarding their complex nature. This has allowed the development of new therapeutic strategies against leukemia. Advances in biotechnology and the current understanding of T cell-engineering have led to new approaches in this fight, thus improving cell-mediated immune response against cancer. However, most of the investigations focus only on conventional cytotoxic cells, while ignoring the potential of unconventional T cells that until now have been little studied. γδ T cells are a unique lymphocyte subpopulation that has an extensive repertoire of tumor sensing and may have new immunotherapeutic applications in a wide range of tumors. The ability to respond regardless of human leukocyte antigen (HLA) expression, the secretion of antitumor mediators and high functional plasticity are hallmarks of γδ T cells, and are ones that make them a promising alternative in the field of cell therapy. Despite this situation, in particular cases, the leukemic microenvironment can adopt strategies to circumvent the antitumor response of these lymphocytes, causing their exhaustion or polarization to a tumor-promoting phenotype. Intervening in this crosstalk can improve their capabilities and clinical applications and can make them key components in new therapeutic antileukemic approaches. In this review, we highlight several characteristics of γδ T cells and their interactions in leukemia. Furthermore, we explore strategies for maximizing their antitumor functions, aiming to illustrate the findings destined for a better mobilization of γδ T cells against the tumor. Finally, we outline our perspectives on their therapeutic applicability and indicate outstanding issues for future basic and clinical leukemia research, in the hope of contributing to the advancement of studies on γδ T cells in cancer immunotherapy.

Lentiviral Vectors for T Cell Engineering: Clinical Applications, Bioprocessing and Future Perspectives

Lentiviral vectors have played a critical role in the emergence of gene-modified cell therapies, specifically T cell therapies. Tisagenlecleucel (Kymriah), axicabtagene ciloleucel (Yescarta) and most recently brexucabtagene autoleucel (Tecartus) are examples of T cell therapies which are now commercially available for distribution after successfully obtaining EMA and FDA approval for the treatment of blood cancers. All three therapies rely on retroviral vectors to transduce the therapeutic chimeric antigen receptor (CAR) into T lymphocytes. Although these innovations represent promising new therapeutic avenues, major obstacles remain in making them readily available tools for medical care. This article reviews the biological principles as well as the bioprocessing of lentiviral (LV) vectors and adoptive T cell therapy. Clinical and engineering successes, shortcomings and future opportunities are also discussed. The development of Good Manufacturing Practice (GMP)-compliant instruments, technologies and protocols will play an essential role in the development of LV-engineered T cell therapies.

Novel strategies for immuno-oncology breakthroughs with cell therapy

Cell therapy has evolved rapidly in the past several years with more than 250 clinical trials ongoing around the world. While more indications of cellular therapy with chimeric antigen receptor – engineered T cells (CAR-T) are approved for hematologic malignancies, new concepts and strategies of cellular therapy for solid tumors are emerging and are discussed. These developments include better selections of targets by shifting from tumor-associated antigens to personalized tumor-specific neoantigens, an enhancement of T cell trafficking by breaking the stromal barriers, and a rejuvenation of exhausted T cells by targeting immunosuppressive mechanisms in the tumor microenvironment (TME). Despite significant remaining challenges, we believe that cell therapy will once again lead and revolutionize cancer immunotherapy before long because of the maturation of technologies in T cell engineering, target selection and T cell delivery. This review highlighted the recent progresses reported at the 2020 China Immuno-Oncology Workshop co-organized by the Chinese American Hematologist and Oncologist Network (CAHON), the China National Medical Product Administration (NMPA), and Tsinghua University.