Cross-reactivity of unwanted T cell response, among other things, due to the selection of non-suitable epitopes may result in elevated off-target effects and lethal toxicity. Therefore, identifying the proper target peptide HLA (pHLA) complex is crucial for generating TCRs for improved safety and efficacy. EXPItope-M, the refined version of EXPItope 2.0, is our improved proprietary tool to assess immunotherapeutic antigens for their potential cross-reactivity against naturally expressed proteins in human tissues.
Immune tolerance, which is also known as central and peripheral tolerance, is the active state of unresponsiveness of the immune system to specific substances or tissues to prevent autoimmune diseases. The process of negative and positive selection play a significant role in the development of central tolerance, where the immune system learns to discriminate between self and non-self. Positive selection is the elimination of T cells lacking proper binding of the T- cell receptor (TCR) to the human leukocyte antigen (HLA). Conversely, negative selection eliminates high-affinity TCRs from the T cell repertoire with a very strong binding to any self-antigens, including cancer-testis antigens (CTAs), to avoid auto-immunity.
Tumor immune escape (“Immune evasion”) is a phenomenon allowing cancer cells to proliferate and metastasize without being recognized by the host immune system. Immune evasion is one of the major challenges in immunotherapy.
Persistent signaling can drive TCR-T cells to mediate inflammatory responses against vital tissues, especially in crucial organs like the brain. Moreover, over-activation or sustained TCR signaling can dampen the therapeutic efficacy leading to T cell exhaustion or cell death. One way to overcome persistent signaling is an inducible system to switch the TCR on and off selectively. Different approaches exist to control engineered T cells. Medigene merges its TCR with the 4OH-Tamoxifen inducible system, one of the best-characterized “reversible switch” models with numerous beneficial features.