Delving into the Latest Updates on artLCMV-TRP2 with Synapse

Author: Hölzel, Michael ; Bald, Tobias ; Stemeseder, Felix ; Lercher, Alexander ; Makky, Ahmad ; Besse, Lenka ; Bomze, David ; Lauterbach, Henning ; Rochwarger, Alexander ; Abdou, Marie-Therese ; Flatz, Lukas ; Ludewig, Burkhard ; Berner, Fiamma ; Schmidt, Sarah ; Palmowski, Yannick A ; Orlinger, Klaus K ; Schietinger, Andrea ; Tüting, Thomas ; Schürch, Christian ; Ring, Sandra S ; Cupovic, Jovana ; Kochanek, Stefan ; Hartmann, Fabienne ; Bergthaler, Andreas ; Purde, Mette-Triin

Harnessing the immune system to eradicate tumors requires identification and targeting of tumor antigens, including tumor-specific neoantigens and tumor-associated self-antigens. Tumor-associated antigens are subject to existing immune tolerance, which must be overcome by immunotherapies. Despite many novel immunotherapies reaching clinical trials, inducing self-antigen-specific immune responses remains challenging. Here, we systematically investigate viral-vector-based cancer vaccines encoding a tumor-associated self-antigen (TRP2) for the treatment of established melanomas in preclinical mouse models, alone or in combination with adoptive T cell therapy. We reveal that, unlike foreign antigens, tumor-associated antigens require replication of lymphocytic choriomeningitis virus (LCMV)-based vectors to break tolerance and induce effective antigen-specific CD8⁺ T cell responses. Immunization with a replicating LCMV vector leads to complete tumor rejection when combined with adoptive TRP2-specific T cell transfer. Importantly, immunization with replicating vectors leads to extended antigen persistence in secondary lymphoid organs, resulting in efficient T cell priming, which renders previously "cold" tumors open to immune infiltration and reprograms the tumor microenvironment to "hot." Our findings have important implications for the design of next-generation immunotherapies targeting solid cancers utilizing viral vectors and adoptive cell transfer.

100 Deals associated with artLCMV-TRP2

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