CAR T cell therapy: A new era for cancer treatment (Review)

Abstract

Cancer has recently been identified as the leading cause of mortality worldwide. Several conventional treatments and cytotoxic immunotherapies have been developed and made available to the market. Considering the complex behavior of tumors and the involvement of numerous genetic and cellular factors involved in tumorigenesis and metastasis, there is a need to develop a promising immunotherapy that targets tumors at both the cellular and genetic levels. Chimeric antigen receptor (CAR) T cell therapy has emerged as a novel therapeutic T cell engineering practice, in which T cells derived from patient blood are engineered in vitro to express artificial receptors targeted to a specific tumor antigen. These directly identify the tumor antigen without the involvement of the major histocompatibility complex. The use of this therapy in the last few years has been successful, with a reduction in remission rates of up to 80% for hematologic cancer, particularly for acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphomas, such as large B cell lymphoma. Recently, anti-CD19 CAR therapy, or UCART19, has been shown to be efficacious in treating relapsed/refractory hematologic cancer. Several other cell surface tumor antigens, such as CD20 and CD22, found in the majority of leukemias and lymphomas are considered potential targets by pharmaceutical companies and research organizations, and trials have been ongoing in this direction. Although this therapeutic regimen is currently confined to treating hematologic cancer, the increasing involvement of several auxiliary techniques, such as bispecific CAR, Tan-CAR, inhibitory-CAR, combined antigens, the clustered regularly interspaced short palindromic repeats gene-editing tool and nanoparticle delivery, may substantially improve its overall anticancer effects. CAR therapy has the potential to offer a rapid and safer treatment regime to treat non-solid and solid tumors. The present review presents an insight into the advantages and the advances of CAR immunotherapy and presents the emerging discrepancy of CAR therapy over usual forms of therapy, such as chemotherapy and radiotherapy. Contents 1. Introduction 2. CAR T cell therapy 3. Architectural ideology of T cell engineering and CAR design 4. Mode of delivery 5. Challenges of CAR T cell therapy 6. Advanced features of CAR T cell therapy 7. Advantages of CAR therapy over other therapies 8. CAR T cell therapy trials for solid tumors 9. Success rates of approved therapies 10. Future prospects

Cancer immunotherapy with γδ T cells: many paths ahead of us

“… 169 Chimeric antigen receptor-modified T (CAR-T) cells that express CAR molecules that target surface antigens on tumor cells have revolutionized the treatment of B-cell malignancies but have yet to achieve the same level of success for solid tumors. 170 γδ T cells are interesting recipient cells for CAR constructs as the transfection should result in effector cells with two-fold antitumor activity, e.g., (i) through the endogenous γδ TCRs and (ii) through the CAR specificity. 171 In fact, CAR-transduced Vδ2T cells showed enhanced cytotoxicity towards relevant tumor target cells.…”

Development of an Immune-Related Risk Signature for Predicting Prognosis in Lung Squamous Cell Carcinoma

“…Patients with LSCC have benefited from an expanding immunotherapies, such as programmed cell death-1 (PD-1)/programmed cell death ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibition, VEGFR inhibition, and targeted therapies matched to fibroblast growth factor receptor (FGFR) and PI3K-AKT ( Derman et al, 2015 ). However, only a small number of patients showed effective remission to immune checkpoint blockade ( Wei et al, 2018 ) or chimeric antigen receptor (CAR) T cell therapy ( Mohanty et al, 2019 ). Identification of strong gene signature to trace the immune status of cancer patients would be vital to establish reliable immune prognostic biomarkers, and to enable stratification of patients into high- and low-risk groups that might be beneficial or responsive to immunotherapy.…”

Advances in Lipid Nanoparticles for mRNA-Based Cancer Immunotherapy

“…CAR T-cell therapy represents the most advanced personalized cancer immunotherapy and has received approval from the FDA and the European Medicine Agency (EMA) for its clinical implementation in the context of hematological cancers, including acute lymphoblastic leukemia and diffuse large Bcell lymphoma (Mohanty et al, 2019;Vitale and Strati, 2020). Thus, CAR T cell therapy is one of the first successful examples of cell engineering and personalized adoptive cell transfer immunotherapy to become available in clinic.…”