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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
T Cell Based Immunotherapy for Cancer: Approaches and Strategies
Muzamil Y Want1, Zeenat Bashir2, Rauf A Najar3
1Department of Immunology, Division of Translational Immuno-Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA.
Abstract:
T cells are critical in destroying cancer cells by recognizing antigens presented by MHC molecules on cancer cells or antigen-presenting cells. Identifying and targeting cancer-specific or overexpressed self-antigens is essential for redirecting T cells against tumors, leading to tumor regression. This is achieved through the identification of mutated or overexpressed self-proteins in cancer cells, which guide the recognition of cancer cells by T-cell receptors. There are two main approaches to T cell-based immunotherapy: HLA-restricted and HLA-non-restricted Immunotherapy. Significant progress has been made in T cell-based immunotherapy over the past decade, using naturally occurring or genetically engineered T cells to target cancer antigens in hematological malignancies and solid tumors. However, limited specificity, longevity, and toxicity have limited success rates. This review provides an overview of T cells as a therapeutic tool for cancer, highlighting the advantages and future strategies for developing effective T cell cancer immunotherapy. The challenges associated with identifying T cells and their corresponding antigens, such as their low frequency, are also discussed. The review further examines the current state of T cell-based immunotherapy and potential future strategies, such as the use of combination therapy and the optimization of T cell properties, to overcome current limitations and improve clinical outcomes.
Insights
T cell immunotherapy redirects T cells to fight cancer by targeting tumor antigens. Future strategies aim to improve specificity, longevity, and reduce toxicity for better cancer treatment outcomes.
Area of Science:
- Immunology
- Oncology
- Biotechnology
Background:
- T cells are crucial for cancer cell destruction via antigen recognition.
- Targeting cancer-specific antigens is key for effective T cell-mediated tumor rejection.
- Current T cell immunotherapies face challenges in specificity, longevity, and toxicity.
Purpose of the Study:
- To review T cells as a therapeutic strategy in cancer immunotherapy.
- To highlight the advantages and future directions for T cell-based cancer treatments.
- To discuss challenges in identifying T cells and their antigens.
Main Methods:
- Review of current literature on T cell-based cancer immunotherapy.
- Analysis of naturally occurring and genetically engineered T cell approaches.
- Examination of strategies to overcome limitations in T cell therapy.
Main Results:
- T cell immunotherapy has shown progress in hematological malignancies and solid tumors.
- Limited antigen specificity, T cell persistence, and toxicity remain significant hurdles.
- Identifying low-frequency T cells and cognate antigens is a major challenge.
Conclusions:
- Optimizing T cell properties and exploring combination therapies are crucial for advancing cancer immunotherapy.
- Future strategies must address current limitations to improve clinical efficacy and patient outcomes.
- Further research is needed to enhance T cell-based cancer treatment effectiveness.
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