Evolution of CD8+ T Cell Receptor (TCR) Engineered Therapies for the Treatment of Cancer

Engineered T cell receptor T (TCR-T) cell therapy has facilitated the generation of increasingly reliable tumor antigen-specific adaptable cellular products for the treatment of human cancer. TCR-T cell therapies were initially focused on targeting shared tumor-associated peptide targets, including...

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Bibliographic Details
Published in:Cells (Basel, Switzerland) Switzerland), 2021-09, Vol.10 (9), p.2379
Main Authors: Sun, Yimo, Li, Fenge, Sonnemann, Heather, Jackson, Kyle R., Talukder, Amjad H., Katailiha, Arjun S., Lizee, Gregory
Format: Article
Language:English
Subjects:
Antigen (tumor-associated)
Antigens
Avidity
Cancer
cancer treatment
CD8 antigen
Cell therapy
Clinical trials
Cloning vectors
Colorectal cancer
engineered TCR-T cell therapy
Immunotherapy
Kinases
Lymphocytes
Lymphocytes T
Melanoma
Neoantigens
Patients
Peptides
Review
Sarcoma
Signal transduction
Solid tumors
T cell receptors
T-cell receptor (TCR)
tumor antigen
Tumors
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Summary:Engineered T cell receptor T (TCR-T) cell therapy has facilitated the generation of increasingly reliable tumor antigen-specific adaptable cellular products for the treatment of human cancer. TCR-T cell therapies were initially focused on targeting shared tumor-associated peptide targets, including melanoma differentiation and cancer-testis antigens. With recent technological developments, it has become feasible to target neoantigens derived from tumor somatic mutations, which represents a highly personalized therapy, since most neoantigens are patient-specific and are rarely shared between patients. TCR-T therapies have been tested for clinical efficacy in treating solid tumors in many preclinical studies and clinical trials all over the world. However, the efficacy of TCR-T therapy for the treatment of solid tumors has been limited by a number of factors, including low TCR avidity, off-target toxicities, and target antigen loss leading to tumor escape. In this review, we discuss the process of deriving tumor antigen-specific TCRs, including the identification of appropriate tumor antigen targets, expansion of antigen-specific T cells, and TCR cloning and validation, including techniques and tools for TCR-T cell vector construction and expression. We highlight the achievements of recent clinical trials of engineered TCR-T cell therapies and discuss the current challenges and potential solutions for improving their safety and efficacy, insights that may help guide future TCR-T studies in cancer.
ISSN:2073-4409
2073-4409
DOI:10.3390/cells10092379