scholarly journals Therapeutic Applications of Engineered Chimeric Antigen Receptors-T cell for Cancer Therapy

2021 ◽  
Author(s):  
Amina Hussain
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Cell Therapy ◽  
Malignant Tumors ◽  
Adoptive Cell Therapy ◽  
Clinical Results ◽  
Antigen Receptors ◽  
Chimeric Antigen Receptors ◽  
T Cell Therapy

Findings of new targeted treatments with adequate safety evaluations is essential for better cancer cures and mortality rates. Immunotherapy holds promise for patients with relapsed disease, with the ability to elicit long-term remissions. Emerging promising clinical results in B-cell malignancy using gene-altered T-lymphocytes uttering chimeric antigen receptors have sparked a lot of interest. This treatment could open the path for a major difference in the way we treat tumors that are resistant or recurring. Genetically altered T cells used to produce tumor-specific chimeric antigen receptors are resurrected field of adoptive cell therapy by demonstrating remarkable success in the treatment of malignant tumors. Because of the molecular complexity of chimeric antigen receptors -T cells, a variety of engineering approaches to improve safety and effectiveness are necessary to realize larger therapeutic uses. In this study, we investigate at new strategies for enhancing chimeric antigen receptors-T cell therapy by altering chimeric antigen receptors proteins, T lymphocytes, and their relations with other solid tumor microenvironment (TME) aspects.

scholarly journals A brief review concerning Chimeric Antigen Receptors T cell therapy

2020 ◽  
Vol 11 (18) ◽  
pp. 5424-5431
Author(s):  
Ling-Lin Li ◽  
Hong-Ling Yuan ◽  
Yu-Qiong Yang ◽  
Lin Wang ◽  
Ren-Chao Zou
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Antigen Receptors ◽  
Chimeric Antigen Receptors ◽  
T Cell Therapy

An Update on Adoptive T-Cell Therapy and Neoantigen Vaccines

2019 ◽  
pp. e70-e78 ◽  
Author(s):  
Patrick A. Ott ◽  
Gianpietro Dotti ◽  
Cassian Yee ◽  
Stephanie L. Goff
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Therapy ◽  
Adoptive Cell Therapy ◽  
Adoptive T Cell Therapy ◽  
Clinical Activity ◽  
Single Chain ◽  
T Cell Therapy ◽  
Substantial Impact ◽  
Mhc Molecules

Adoptive T-cell therapy using tumor-infiltrating lymphocytes (TILs) has demonstrated long-lasting antitumor activity in select patients with advanced melanoma. Cancer vaccines have been used for many decades and have shown some promise but overall relatively modest clinical activity across cancers. Technological advances in genome sequencing capabilities and T-cell engineering have had substantial impact on both adoptive cell therapy and the cancer vaccine field. The ability to identify neoantigens—a class of tumor antigens that is truly tumor specific and encoded by tumor mutations through rapid and relatively inexpensive next-generation sequencing—has already demonstrated the critical importance of these antigens as targets of antitumor-specific T-cell responses in the context of immune checkpoint blockade and other immunotherapies. Therapeutically targeting these antigens with either adoptive T-cell therapy or vaccine approaches has demonstrated early promise in the clinic in patients with advanced solid tumors. Chimeric antigen receptor (CAR) T cells, which are engineered by fusing an antigen-specific, single-chain antibody (scFv) with signaling molecules of the T-cell receptor (TCR)/CD3 complex creating an antibody-like structure on T cells that recognizes antigens independently of major histocompatibility complex (MHC) molecules, have demonstrated remarkable clinical activity in patients with advanced B-cell malignancies, leading to several approvals by the U.S. Food and Drug Administration (FDA).

Abstract 3238: Engineering chimeric antigen receptors for adoptive T cell therapy of cancers that express the Tn antigen

2020 ◽  
Author(s):  
Preeti Sharma ◽  
Venkata VVR Marada ◽  
Monika Kizerwetter ◽  
Claire P. Schane ◽  
Yanran He ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Adoptive T Cell Therapy ◽  
Antigen Receptors ◽  
Tn Antigen ◽  
Chimeric Antigen Receptors ◽  
T Cell Therapy

scholarly journals Fully human CD19-specific chimeric antigen receptors for T-cell therapy

Leukemia ◽  
2017 ◽  
Vol 31 (10) ◽  
pp. 2191-2199 ◽  
Author(s):  
D Sommermeyer ◽  
T Hill ◽  
S M Shamah ◽  
A I Salter ◽  
Y Chen ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Antigen Receptors ◽  
Chimeric Antigen Receptors ◽  
T Cell Therapy

IL-7 and IL-15 instruct the generation of human memory stem T cells from naive precursors

Blood ◽  
2013 ◽  
Vol 121 (4) ◽  
pp. 573-584 ◽  
Author(s):  
Nicoletta Cieri ◽  
Barbara Camisa ◽  
Fabienne Cocchiarella ◽  
Mattia Forcato ◽  
Giacomo Oliveira ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Therapy ◽  
Adoptive Cell Therapy ◽  
Cell Subset ◽  
Gene Expression Signature ◽  
Adoptive T Cell Therapy ◽  
T Cell Therapy ◽  
Hematopoietic Stem ◽  
T Cell Subset

Abstract Long-living memory stem T cells (TSCM) with the ability to self-renew and the plasticity to differentiate into potent effectors could be valuable weapons in adoptive T-cell therapy against cancer. Nonetheless, procedures to specifically target this T-cell population remain elusive. Here, we show that it is possible to differentiate in vitro, expand, and gene modify in clinically compliant conditions CD8+ TSCM lymphocytes starting from naive precursors. Requirements for the generation of this T-cell subset, described as CD62L+CCR7+CD45RA+CD45R0+IL-7Rα+CD95+, are CD3/CD28 engagement and culture with IL-7 and IL-15. Accordingly, TSCM accumulates early after hematopoietic stem cell transplantation. The gene expression signature and functional phenotype define this population as a distinct memory T-lymphocyte subset, intermediate between naive and central memory cells. When transplanted in immunodeficient mice, gene-modified naive-derived TSCM prove superior to other memory lymphocytes for the ability to expand and differentiate into effectors able to mediate a potent xenogeneic GVHD. Furthermore, gene-modified TSCM are the only T-cell subset able to expand and mediate GVHD on serial transplantation, suggesting self-renewal capacity in a clinically relevant setting. These findings provide novel insights into the origin and requirements for TSCM generation and pave the way for their clinical rapid exploitation in adoptive cell therapy.

scholarly journals CAR T-cell therapy for glioblastoma: recent clinical advances and future challenges

2018 ◽  
Vol 20 (11) ◽  
pp. 1429-1438 ◽  
Author(s):  
Stephen J Bagley ◽  
Arati S Desai ◽  
Gerald P Linette ◽  
Carl H June ◽  
Donald M O’Rourke
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Therapy ◽  
Hematologic Malignancies ◽  
Antigen Receptors ◽  
T Cell Therapy ◽  
Car T Cells ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

Abstract In patients with certain hematologic malignancies, the use of autologous T cells genetically modified to express chimeric antigen receptors (CARs) has led to unprecedented clinical responses. Although progress in solid tumors has been elusive, recent clinical studies have demonstrated the feasibility and safety of CAR T-cell therapy for glioblastoma. In addition, despite formidable barriers to T-cell localization and effector function in glioblastoma, signs of efficacy have been observed in select patients. In this review, we begin with a discussion of established obstacles to systemic therapy in glioblastoma and how these may be overcome by CAR T cells. We continue with a summary of previously published CAR T-cell trials in GBM, and end by outlining the key therapeutic challenges associated with the use of CAR T cells in this disease.

scholarly journals Chimeric Antigen Receptor-T Cells: A Pharmaceutical Scope

2021 ◽  
Vol 12 ◽  
Author(s):  
Alejandrina Hernández-López ◽  
Mario A. Téllez-González ◽  
Paul Mondragón-Terán ◽  
Angélica Meneses-Acosta
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Therapy ◽  
Adoptive Cell Therapy ◽  
Genetically Engineered ◽  
First Line ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Advanced Therapy ◽  
Car T

Cancer is among the leading causes of death worldwide. Therefore, improving cancer therapeutic strategies using novel alternatives is a top priority on the contemporary scientific agenda. An example of such strategies is immunotherapy, which is based on teaching the immune system to recognize, attack, and kill malignant cancer cells. Several types of immunotherapies are currently used to treat cancer, including adoptive cell therapy (ACT). Chimeric Antigen Receptors therapy (CAR therapy) is a kind of ATC where autologous T cells are genetically engineered to express CARs (CAR-T cells) to specifically kill the tumor cells. CAR-T cell therapy is an opportunity to treat patients that have not responded to other first-line cancer treatments. Nowadays, this type of therapy still has many challenges to overcome to be considered as a first-line clinical treatment. This emerging technology is still classified as an advanced therapy from the pharmaceutical point of view, hence, for it to be applied it must firstly meet certain requirements demanded by the authority. For this reason, the aim of this review is to present a global vision of different immunotherapies and focus on CAR-T cell technology analyzing its elements, its history, and its challenges. Furthermore, analyzing the opportunity areas for CAR-T technology to become an affordable treatment modality taking the basic, clinical, and practical aspects into consideration.

scholarly journals Developing T-cell therapies for lymphoma without receptor engineering

Hematology ◽  
2017 ◽  
Vol 2017 (1) ◽  
pp. 622-631 ◽  
Author(s):  
Melanie Grant ◽  
Catherine M. Bollard
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Ex Vivo ◽  
Disease Stage ◽  
Antigen Receptors ◽  
Chimeric Antigen Receptors ◽  
T Cell Therapy ◽  
Cell Therapies ◽  
Cell Therapeutics ◽  
Clinical Responses

AbstractT-cell therapy has emerged from the bench for the treatment of patients with lymphoma. Responses to T-cell therapeutics are regulated by multiple factors, including the patient’s immune system status and disease stage. Outside of engineering of chimeric antigen receptors and artificial T-cell receptors, T-cell therapy can be mediated by ex vivo expansion of antigen-specific T cells targeting viral and/or nonviral tumor-associated antigens. These approaches are contributing to enhanced clinical responses and overall survival. In this review, we summarize the available T-cell therapeutics beyond receptor engineering for the treatment of patients with lymphoma.

TCR-engineered T-cell therapy through personalized identification of CDR3 clonotypes.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15021-e15021
Author(s):  
Zishan Zhou ◽  
Yue Pu ◽  
Shanshan Xiao ◽  
Ping Wang ◽  
Yang Yu ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Therapy ◽  
Single Cell ◽  
Adoptive Cell Therapy ◽  
Cell Receptor ◽  
Illumina Hiseq ◽  
T Cell Therapy ◽  
Engineered T Cells

e15021 Background: T-cell receptor (TCR)-engineered T cells are a novel option for adoptive cell therapy used for the treatment of several advanced forms of cancers. Unlike many shared tumor-specific antigens, such as melanoma-associated antigen (MAGE)-A3, MAGE-A4, and New York esophageal squamous cell carcinoma (NY-ESO)-1, neoantigen has garnered much attention as a potential precision immunotherapy. Personalized neoantigen selection serves a broader and more precision future for cancer patients. Methods: Dendritic cells (DCs) derived from adherent monocytes were pulsed with mixed peptides during the maturation phase. CD8+ cells positively selected from PBMCs were incubated with washed DCs. After 21day culture in X-VIVO medium with IL-7 and IL-15, cells were harvested and stimulated with peptides for 6 h. CD137+ cells were sorted by flow cytometric and immediately processed using the 10x Genomic Chromium Single Cell 5' Library & Gel Bead Kit and Chromium Single Cell V(D)J Enrichment Kit. The T-cell TCR libraries were constructed and sequenced on the Illumina HiSeq X Ten platform. The sequencing reads were aligned to the hg38 human reference genome and analyzed using the 10x Genomics Cell Ranger pipeline. The paired TCR α and β chain sequence of each cell was demonstrated with V(D)J analysis. TCR-T cells were constructed using the information of neoantigen specific TCR, and infused to patients. Results: Two patients were treated with the personalized TCR-T treatment. At the first stage, specialized immune cells were harvested and proceeded to single-cell TCR profiling. Then, the single cell sequencing of the first patient's sample revealed the top five neoantigen specific TCR CDR3 clonotypes with the proportion of 25%, 7.67%, 4.81%, 2.79%, and 2.54%, respectively. Similarly, the other patient had the top five TCR CDR3 sequenced with the proportion of 13.38%, 7.04%, 4.21%, 2.83%, and 1.94%, respectively. The results demonstrated that both patients had one or two dominant CDR3 clonotypes, which might reflect the strength of neoantigen in vivo. At the third stage, TCR-T cells were constructed, and infused to the patients. The clinical outcome will be evaluated in the near future. Conclusions: We have generated a pipeline for a highly personalized cancer therapy using TCR-engineered T cells. Although some questions remain to be answered, this novel approach may result in better clinical responses in future treatment.

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