Genetically Engineered T Cells and Recombinant Antibodies to Target Intracellular Neoantigens: Current Status and...

Area of Science:

• Immunology
• Oncology
• Cell Therapy

Background:

• Recombinant antibodies and T cell receptor (TCR)-engineered T cell therapies are emerging as key strategies for targeting intracellular neoantigens in various diseases.
• T cell-based therapies utilize engineered T cells expressing complete TCRs (TCR-T cells), TCR-based chimeric antigen receptors (TCR-CAR-T cells), or TCR-like antibodies (TCR-like CAR-T cells).
• Novel constructs like synthetic T cell receptor and antigen receptor (STAR) and heterodimeric TCR-like CAR (T-CAR) are being developed for enhanced TCR signaling.

Purpose of the Study:

• To review current immunological strategies for targeting intracellular neoantigens.
• To discuss the advantages and limitations of recombinant T cell therapies and antibody-based approaches.
• To explore potential enhancements for T cell therapies to improve clinical efficacy.

Main Methods:

• Review of recombinant antibody and T cell receptor (TCR)-engineered T cell therapy strategies.
• Analysis of different T cell-based therapeutic constructs (TCR-T, TCR-CAR-T, TCR-like CAR-T, STAR, T-CAR).
• Discussion of antibody-based approaches (anti-neopeptide MHC antibodies, intrabodies) and their limitations.

Main Results:

• Recombinant T cells and antibody-based therapies offer distinct mechanisms for targeting intracellular neoantigens.
• Limitations include neoantigen loss, altered antigen presentation, tumor heterogeneity, and immunosuppression.
• Advanced engineering tools like CRISPR/Cas9 and immune checkpoint blockade can potentially overcome these challenges.

Conclusions:

• T cell receptor (TCR)-engineered T cell therapies and recombinant antibodies represent significant advancements in targeting intracellular neoantigens.
• Addressing limitations such as tumor heterogeneity and immunosuppression is crucial for clinical success.
• The integration of genome editing and immune checkpoint inhibitors holds promise for optimizing T cell therapies for routine clinical use.