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Cell Therapy for Colorectal Cancer: The Promise of Chimeric Antigen Receptor (CAR)-T Cells
Cristina Aparicio1, Marina Belver1, Lucía Enríquez1
1Unidad de Excelencia Instituto de Biología y Genética Molecular (IBGM), University of Valladolid (UVa)-CSIC, 47003 Valladolid, Spain.
Abstract:
Colorectal cancer (CRC) is a global public health problem as it is the third most prevalent and the second most lethal cancer worldwide. Major efforts are underway to understand its molecular pathways as well as to define the tumour-associated antigens (TAAs) and tumour-specific antigens (TSAs) or neoantigens, in order to develop an effective treatment. Cell therapies are currently gaining importance, and more specifically chimeric antigen receptor (CAR)-T cell therapy, in which genetically modified T cells are redirected against the tumour antigen of interest. This immunotherapy has emerged as one of the most promising advances in cancer treatment, having successfully demonstrated its efficacy in haematological malignancies. However, in solid tumours, such as colon cancer, it is proving difficult to achieve the same results due to the shortage of TSAs, on-target off-tumour effects, low CAR-T cell infiltration and the immunosuppressive microenvironment. To address these challenges in CRC, new approaches are proposed, including combined therapies, the regional administration of CAR-T cells and more complex CAR structures, among others. This review comprehensively summarises the current landscape of CAR-T cell therapy in CRC from the potential tumour targets to the preclinical studies and clinical trials, as well as the limitations and future perspectives of this novel antitumour strategy.
Insights
Chimeric antigen receptor (CAR)-T cell therapy shows promise for colorectal cancer (CRC). Challenges in solid tumors are being addressed with new strategies for effective CAR-T cell treatments.
Area of Science:
- Oncology
- Immunotherapy
- Cell Therapy
Background:
- Colorectal cancer (CRC) is a leading global cause of cancer-related death.
- Understanding CRC molecular pathways and identifying tumor antigens is crucial for effective treatment.
- Chimeric antigen receptor (CAR)-T cell therapy is a promising immunotherapy approach.
Purpose of the Study:
- To review the current status of CAR-T cell therapy for colorectal cancer.
- To discuss potential tumor targets, preclinical studies, and clinical trials.
- To identify limitations and future directions for CAR-T cell therapy in CRC.
Main Methods:
- Comprehensive literature review of CAR-T cell therapy in colorectal cancer.
- Analysis of studies focusing on tumor antigens, CAR-T cell efficacy, and challenges.
- Examination of preclinical and clinical trial data.
Main Results:
- CAR-T cell therapy has shown success in hematological malignancies but faces challenges in solid tumors like CRC.
- Key challenges in CRC include a shortage of tumor-specific antigens (TSAs), on-target off-tumor effects, and an immunosuppressive tumor microenvironment.
- New strategies like combination therapies and regional CAR-T cell administration are being explored.
Conclusions:
- CAR-T cell therapy holds potential for colorectal cancer treatment.
- Overcoming challenges in solid tumors requires innovative approaches and further research.
- Future directions involve refining CAR-T cell designs and therapeutic strategies for CRC.
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