Harnessing the Power of TSC-101: Pioneering Immunotherapy for Post-Transplant Leukemia

Approximately half of AML patients experience relapse post allogeneic hematopoietic stem cell transplant, resulting in limited treatment options. However, a rare group of patients who develop a specific T cell response against minor antigens exhibit significantly lower relapse rates. HA-2, a minor histocompatibility antigen, is derived from the class I myosin protein and has been identified as a promising target for T cell immunotherapy.

Utilizing TScan's ReceptorScan technology, 1,302 HA-2-specific TCRs were identified from 237 million naive CD8+ T cells of healthy donors lacking HA-2. These TCRs were then evaluated through the DexScan platform, leading to the selection of 15 with the highest surface expression and affinity for the HA-2 peptide. Following individual testing for various characteristics such as surface expression, cytotoxicity, cytokine production, and proliferation, the top 5 TCRs were further scrutinized for alloreactivity and off-target cross-reactivity.

The lead TCR, TSC-101, demonstrated minimal alloreactivity and a narrow off-target profile. Its avidity for potential off-targets was measured to assess toxicity risks, showing extremely weak avidities, suggesting a low risk of toxicity. Consequently, TSC-101 has been selected for IND-enabling activities with the aim of initiating human trials in 2022. This marks the first development of a clinical-grade HA-2-specific TCR for the immunotherapy of liquid tumors.