Neoantigen-targeted TCR-engineered T cell immunotherapy: current advances and challenges

Area of Science:

• Immunology and Cancer Therapy
• Cellular and Molecular Oncology

Background:

• Adoptive cell therapy utilizing T cell receptor-engineered T cells (TCR-T) is a developing cancer treatment strategy.
• TCR-T therapy aims to leverage the natural T cell receptor (TCR) diversity to target tumor-specific antigens.
• Current clinical outcomes for TCR-T therapies, particularly in solid tumors, remain suboptimal, indicating significant challenges.

Purpose of the Study:

• To review TCR structure-based antigen recognition and signaling mechanisms.
• To describe recent advancements in neoantigen identification and specific TCR screening technologies.
• To summarize ongoing clinical trials and discuss challenges and future directions for personalized TCR-T therapy.

Main Methods:

• Review of existing literature on TCR structure, antigen recognition, and signaling pathways.
• Analysis of recent technological advancements in neoantigen discovery and TCR screening.
• Compilation and summary of data from ongoing clinical trials involving TCR-T therapies against neoantigens.

Main Results:

• TCR-T therapy faces hurdles in efficiently screening tumor-specific antigens and their corresponding TCRs.
• Key challenges include viral vector safety, TCR mismatch, and the immunosuppressive tumor microenvironment.
• Progress has been made in understanding TCR-antigen interactions and developing screening technologies.

Conclusions:

• Personalized TCR-T therapy holds significant potential for cancer treatment.
• Overcoming challenges related to antigen discovery, TCR specificity, and the tumor microenvironment is crucial for therapeutic success.
• Future research should focus on innovative strategies to enhance the efficacy and safety of TCR-T cell-based immunotherapies.