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A Nonviral Approach to Generate Transient Chimeric Antigen Receptor T Cells Using mRNA for Cancer Immunotherapy
Published on: February 21, 2025
CAR T cell therapy: A new era for cancer treatment (Review)
Rimjhim Mohanty1, Chitran Roy Chowdhury1, Solomon Arega1
1Cancer Biology Laboratory, School of Biotechnology, Kalinga Institute of Industrial Technology (KIIT) University, Bhubaneswar, Odisha 751024, India.
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.
Insights
Chimeric antigen receptor (CAR) T-cell therapy engineers patient T-cells to target cancer antigens, showing high remission rates for blood cancers. Advances aim to expand CAR therapy
Area of Science:
- Immunology
- Oncology
- Biotechnology
Background:
- Cancer is a leading global cause of death, necessitating advanced treatments.
- Conventional therapies face limitations due to tumor complexity and genetic factors.
- Chimeric antigen receptor (CAR) T-cell therapy offers a novel approach to target tumors.
Purpose of the Study:
- To review the advantages and advancements in CAR T-cell immunotherapy.
- To highlight the potential of CAR therapy over conventional treatments like chemotherapy and radiotherapy.
- To discuss the emerging applications and future directions of CAR T-cell therapy.
Main Methods:
- Engineering patient-derived T-cells in vitro to express CARs targeting specific tumor antigens.
- Utilizing CARs that recognize tumor antigens independently of the major histocompatibility complex.
- Reviewing clinical data and ongoing research on CAR T-cell therapy efficacy.
Main Results:
- CAR T-cell therapy has achieved remission rates up to 80% in hematologic cancers, including ALL and lymphomas.
- Anti-CD19 CAR therapy (UCART19) demonstrates efficacy in relapsed/refractory hematologic malignancies.
- CD20 and CD22 are identified as promising targets for CAR therapy in leukemias and lymphomas.
Conclusions:
- CAR T-cell therapy represents a significant advancement in cancer immunotherapy.
- Ongoing research and auxiliary techniques may expand CAR therapy's application to solid tumors.
- CAR therapy shows potential for rapid and safer cancer treatment compared to traditional methods.

