Genetically Engineered T cells and Recombinant Antibodies to Target Intracellular Neoantigens: Current Status and Future Directions

Immunotherapy, particularly through the use of recombinant antibodies and T cell receptor (TCR) engineered T-cell therapies, has significantly advanced the targeting of intracellular neoantigens in both benign and malignant diseases. These therapies, including TCR-T cells, TCR chimeric antigen receptor T-cells (TCR-CAR T-cells), and TCR-like CAR T-cells, leverage the specificity of TCRs to recognize and attack tumor cells presenting neoantigens. Additionally, modalities like STAR and T-CARS employ double-chain TCRαβ-based receptors that mimic natural TCR signaling, further enhancing therapeutic efficacy. Despite their potential, challenges such as antigen variability, tumor heterogeneity, and an immunosuppressive tumor microenvironment persist, impacting the efficacy and application of these therapies.

This Research Topic aims to conduct a thorough comparison of the current T cell therapies and recombinant antibody therapies, elucidating their respective advantages and disadvantages in clinical settings. It seeks to address how these therapies can be optimized for better specificity and efficacy, and how emerging technologies like CRISPR/Cas9, immune checkpoint inhibitors and mRNA delivery systems can be integrated to overcome existing limitations.

To gather further insights into these innovative therapies, we welcome articles addressing, but not limited to, the following themes:
o T cells and TCR-T-cell therapy
o Innovations in STAR, T-CARs and TCR-CAR T-cell formats
o TCR-like CAR-T cells
o Developments in recombinant antibodies targeting MHC/neopeptide complexes
o Bispecific antibodies formats like CD3 x TCR-like antibody and CD3 x TCR antibody
o Intrabodies and their role in neutralizing intra-tumoral neoantigens
o CD8+ T cell therapy advancements and challenges (e.g. CD8-fit T cells)
o Harnessing and modulating the tumor microenvironment to boost adoptive T cell therapy


Please note that manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by robust and relevant validation (clinical cohort or biological validation in vitro or in vivo) are out of scope for this Research Topic.