Adoptive cell therapy for cancer using T-cells genetically engineered to express chimeric antigen receptors

2017 ◽  
pp. 591-601
Author(s):  
Sarwish Rafiq ◽  
Renier J. Brentjens
Keyword(s):  
T Cells ◽  
Cell Therapy ◽  
Adoptive Cell Therapy ◽  
Genetically Engineered ◽  
Antigen Receptors ◽  
Chimeric Antigen Receptors

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 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 Chimeric antigen receptor–modified T cells: CD19 and the road beyond

Blood ◽  
2018 ◽  
Vol 131 (24) ◽  
pp. 2621-2629 ◽  
Author(s):  
Alexander I. Salter ◽  
Margot J. Pont ◽  
Stanley R. Riddell
Keyword(s):  
T Cells ◽  
Cell Therapy ◽  
Adoptive Cell Therapy ◽  
Hematologic Malignancies ◽  
Current Status ◽  
Antigen Receptors ◽  
T Cell Therapy ◽  
Ongoing Research ◽  
The Road ◽  
Car T

Abstract The ability to harness a patient’s immune system to target malignant cells is now transforming the treatment of many cancers, including hematologic malignancies. The adoptive transfer of T cells selected for tumor reactivity or engineered with natural or synthetic receptors has emerged as an effective modality, even for patients with tumors that are refractory to conventional therapies. The most notable example of adoptive cell therapy is with T cells engineered to express synthetic chimeric antigen receptors (CARs) that reprogram their specificity to target CD19. CAR T cells have shown remarkable antitumor activity in patients with refractory B-cell malignancies. Ongoing research is focused on understanding the mechanisms of incomplete tumor elimination, reducing toxicities, preventing antigen escape, and identifying suitable targets and strategies based on established and emerging principles of synthetic biology for extending this approach to other hematologic malignancies. This review will discuss the current status, challenges, and potential future applications of CAR T-cell therapy in hematologic malignancies.

scholarly journals Adoptive Cell Therapy—Harnessing Antigen-Specific T Cells to Target Solid Tumours

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 683 ◽  
Author(s):  
Elżbieta Chruściel ◽  
Zuzanna Urban-Wójciuk ◽  
Łukasz Arcimowicz ◽  
Małgorzata Kurkowiak ◽  
Jacek Kowalski ◽  
...  
Keyword(s):  
T Cells ◽  
Adoptive Cell Therapy ◽  
Solid Tumours ◽  
Great Success ◽  
Antigen Receptors ◽  
Chimeric Antigen Receptors ◽  
Cell Therapies ◽  
Alternative Approaches ◽  
Therapeutic Tools ◽  
Infiltrating Lymphocytes

In recent years, much research has been focused on the field of adoptive cell therapies (ACT) that use native or genetically modified T cells as therapeutic tools. Immunotherapy with T cells expressing chimeric antigen receptors (CARs) demonstrated great success in the treatment of haematologic malignancies, whereas adoptive transfer of autologous tumour infiltrating lymphocytes (TILs) proved to be highly effective in metastatic melanoma. These encouraging results initiated many studies where ACT was tested as a treatment for various solid tumours. In this review, we provide an overview of the challenges of T cell-based immunotherapies of solid tumours. We describe alternative approaches for choosing the most efficient T cells for cancer treatment in terms of their tumour-specificity and phenotype. Finally, we present strategies for improvement of anti-tumour potential of T cells, including combination therapies.

scholarly journals Adoptive Cell Therapy—Tumor-Infiltrating Lymphocytes, T-Cell Receptors, and Chimeric Antigen Receptors

2015 ◽  
Vol 42 (4) ◽  
pp. 626-639 ◽  
Author(s):  
Steven A. Feldman ◽  
Yasmine Assadipour ◽  
Isaac Kriley ◽  
Stephanie L. Goff ◽  
Steven A. Rosenberg
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
T Cell Receptors ◽  
Adoptive Cell Therapy ◽  
Tumor Infiltrating Lymphocytes ◽  
Antigen Receptors ◽  
Chimeric Antigen Receptors ◽  
Cell Receptors ◽  
Infiltrating Lymphocytes

scholarly journals Genetically engineered T cells for cancer immunotherapy

2019 ◽  
Vol 4 (1) ◽  
Author(s):  
Dan Li ◽  
Xue Li ◽  
Wei-Lin Zhou ◽  
Yong Huang ◽  
Xiao Liang ◽  
...  
Keyword(s):  
T Cells ◽  
Cancer Immunotherapy ◽  
Hematological Malignancies ◽  
Genetically Engineered ◽  
Immune Checkpoints ◽  
Antigen Receptors ◽  
Chimeric Antigen Receptors ◽  
Recognition Method ◽  
Engineered T Cells ◽  
Mutant Cells

Abstract T cells in the immune system protect the human body from infection by pathogens and clear mutant cells through specific recognition by T cell receptors (TCRs). Cancer immunotherapy, by relying on this basic recognition method, boosts the antitumor efficacy of T cells by unleashing the inhibition of immune checkpoints and expands adaptive immunity by facilitating the adoptive transfer of genetically engineered T cells. T cells genetically equipped with chimeric antigen receptors (CARs) or TCRs have shown remarkable effectiveness in treating some hematological malignancies, although the efficacy of engineered T cells in treating solid tumors is far from satisfactory. In this review, we summarize the development of genetically engineered T cells, outline the most recent studies investigating genetically engineered T cells for cancer immunotherapy, and discuss strategies for improving the performance of these T cells in fighting cancers.

scholarly journals AIM Platform: A Novel Nano Artificial Antigen-Presenting Cell-Based Clinical System Designed to Consistently Produce Multi-Antigen-Specific T-Cell Products with Potent and Durable Anti-Tumor Properties

2020 ◽  
Vol 47 (6) ◽  
pp. 464-471
Author(s):  
Lauren Suarez ◽  
Ruipeng Wang ◽  
Scott Carmer ◽  
Daniel Bednarik ◽  
Han Myint ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Dendritic Cell ◽  
Cell Therapy ◽  
Ex Vivo ◽  
Adoptive Cell Therapy ◽  
Tumor Infiltrating Lymphocytes ◽  
Genetically Engineered ◽  
Alternative Methods ◽  
Cell Repertoire

Over the last decade, tremendous progress has been made in the field of adoptive cell therapy. The two prevailing modalities include endogenous non-engineered approaches and genetically engineered T-cell approaches. Endogenous non-engineered approaches include dendritic cell-based systems and tumor-infiltrating lymphocytes (TIL) that are used to produce multi-antigen-specific T-cell products. Genetically engineered approaches, such as T-cell receptor engineered cells and chimeric antigen receptor T cells are used to produce single antigen-specific T-cell products. It is noted by the authors that there are alternative methods to sort for antigen-specific T cells such as peptide multimer sorting or cytokine secretion assay-based sorting, both of which are potentially challenging for broad development and commercialization. In this review, we are focusing on a novel nanoparticle technology that generates a non-engineered product from the endogenous T-cell repertoire. The most common approaches for ex vivo activation and expansion of endogenous, non-genetically engineered cell therapy products rely on dendritic cell-based systems or IL-2 expanded TIL. Hurdles remain in developing efficient, consistent, controlled processes; thus, these processes still have limited access to broad patient populations. Here, we describe a novel approach to produce cellular therapies at clinical scale, using proprietary nanoparticles combined with a proprietary manufacturing process to enrich and expand antigen-specific CD8<sup>+</sup> T-cell products with consistent purity, identity, and composition required for effective and durable anti-tumor response.

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