The treatment with recombinant antibodies and more recently T cell receptor (TCR) engineered T-cell therapies represent two immunological strategies that came into the forefront of clinical interest for targeting intracellular neoantigens in benign and malignant diseases. T cell based therapies targeting neoantigens use T cells expressing a recombinant complete TCR (TCR-T-cell), a chimeric antigen receptor with the variable domains of a neo-epitope-reactive TCR as a binding domain (TCR-CAR T-cell) or a TCR-like antibody as a binding domain (TCR-like-CAR T-cell). Furthermore STAR and T-CARS are designed as a double-chain TCR-based receptor with variable regions of immunoglobulin heavy and light chains (VH and VL) fused to TCR-C and TCR-C, respectively resulting in TCR signaling. In contrast to the use of recombinant T cells, anti-neopeptide MHC antibodies can be easier applied to cancer patients. The recombinant antibodies targeting MHC/neopeptide complexes include TCR-like antibodies, bispecific antibodies in the format CD3 x TCR-like antibody or CD3 x soluble TCR. In addition, intrabodies are able to neutralize neoantigens inside tumor cells. These developments are becoming intensified through the identification of new neopeptide/MHC complexes with cognate TCRs by screening the T cell repertoire of healthy donors and cancer patients with dendritic cells presenting the predicted neopeptide/MHC complex or by screening a personalized CD8+ T cell library with soluble neoantigen-MHC capture reagents. Interestingly, lipid nanoparticles carrying therapeutic mRNA have become a practical tool for the targeted in vivo delivery of TCRs, TCR CARs, TCR-like CARs, bispecific antibodies and intrabodies. However, different limitations should be considered, such as the loss of neoantigens, the modification of antigen peptide presentation, tumor heterogenicity, and the immunosuppressive activity of the tumor environment. Together with the simultaneous application of immune checkpoint blocking antibodies and of CRISPR/Cas9 based-genome-editing tools to engineer different recombinant T cells with enhanced therapeutic functions could make these CAR T cell therapies more efficient and could pave the way for its routine clinical application in the future.
In this collection, we wish to compare the advantages and disadvantages of the actually T cell therapies. We will welcome all types of articles dealing with, but not limited to, the following topics: T cells, TCR-T-cell , STAR, TCR-CAR T-cell, TCR like CAR-T cells, recombinant antibodies targeting MHC/neopeptide complexes, bispecific antibodies in the format CD3 x TCR-like antibody or CD3 x soluble TCR, intrabodies, and CD8+ 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.
Keywords:
Neoantigens, TCR like antibodies, intrabodies, bispecific antibody (CD3 x TCR, CD3 x TCR like antibody), TCR CARs, TCR like CARs, T-CARs, STARs, therapeutic mRNA, checkpoint blocking antibodies, CRISPR/Cas9 based-genome-editing
Important Note:
All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.
The treatment with recombinant antibodies and more recently T cell receptor (TCR) engineered T-cell therapies represent two immunological strategies that came into the forefront of clinical interest for targeting intracellular neoantigens in benign and malignant diseases. T cell based therapies targeting neoantigens use T cells expressing a recombinant complete TCR (TCR-T-cell), a chimeric antigen receptor with the variable domains of a neo-epitope-reactive TCR as a binding domain (TCR-CAR T-cell) or a TCR-like antibody as a binding domain (TCR-like-CAR T-cell). Furthermore STAR and T-CARS are designed as a double-chain TCR-based receptor with variable regions of immunoglobulin heavy and light chains (VH and VL) fused to TCR-C and TCR-C, respectively resulting in TCR signaling. In contrast to the use of recombinant T cells, anti-neopeptide MHC antibodies can be easier applied to cancer patients. The recombinant antibodies targeting MHC/neopeptide complexes include TCR-like antibodies, bispecific antibodies in the format CD3 x TCR-like antibody or CD3 x soluble TCR. In addition, intrabodies are able to neutralize neoantigens inside tumor cells. These developments are becoming intensified through the identification of new neopeptide/MHC complexes with cognate TCRs by screening the T cell repertoire of healthy donors and cancer patients with dendritic cells presenting the predicted neopeptide/MHC complex or by screening a personalized CD8+ T cell library with soluble neoantigen-MHC capture reagents. Interestingly, lipid nanoparticles carrying therapeutic mRNA have become a practical tool for the targeted in vivo delivery of TCRs, TCR CARs, TCR-like CARs, bispecific antibodies and intrabodies. However, different limitations should be considered, such as the loss of neoantigens, the modification of antigen peptide presentation, tumor heterogenicity, and the immunosuppressive activity of the tumor environment. Together with the simultaneous application of immune checkpoint blocking antibodies and of CRISPR/Cas9 based-genome-editing tools to engineer different recombinant T cells with enhanced therapeutic functions could make these CAR T cell therapies more efficient and could pave the way for its routine clinical application in the future.
In this collection, we wish to compare the advantages and disadvantages of the actually T cell therapies. We will welcome all types of articles dealing with, but not limited to, the following topics: T cells, TCR-T-cell , STAR, TCR-CAR T-cell, TCR like CAR-T cells, recombinant antibodies targeting MHC/neopeptide complexes, bispecific antibodies in the format CD3 x TCR-like antibody or CD3 x soluble TCR, intrabodies, and CD8+ 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.
Keywords:
Neoantigens, TCR like antibodies, intrabodies, bispecific antibody (CD3 x TCR, CD3 x TCR like antibody), TCR CARs, TCR like CARs, T-CARs, STARs, therapeutic mRNA, checkpoint blocking antibodies, CRISPR/Cas9 based-genome-editing
Important Note:
All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.