Personalized SNAP™-TIL platform achieves 70% melanoma, 50% pancreatic tumor growth inhibition in xenograft models.

Traditional Tumor-Infiltrating Lymphocyte (TIL) therapy shows promise in melanoma, but its efficacy is limited in less immunogenic malignancies due to rare or exhausted neoantigen-reactive T-cells. The success of TIL therapy hinges on recognizing tumor-associated antigens, yet current methods often fail to efficiently isolate T-cells enriched for specific neoantigen reactivity. This gap necessitates improved strategies for neoantigen prediction and validation, particularly for HLA class II proteins, to enhance TIL therapy's broader applicability and response rates across diverse cancer types.

Researchers developed the SNAP™ (Specific Neo-Antigen Peptides) technology platform to improve neoantigen prediction and validation. This platform combines advanced computational modeling with PepSeq, a high-throughput screen for credentialing neoantigens based on their affinity to patient-specific HLA class II proteins. This approach allows for the 'education' and enrichment of TILs (SNAP-TILs) with personalized, predefined, highly immunogenic neoantigens prior to in vitro expansion. The efficacy of these SNAP-TILs was then evaluated in ex vivo models and patient-derived xenograft models of melanoma and pancreatic cancer, comparing them against TILs expanded by a rapid expansion protocol alone.

The SNAP™ platform consistently produced a SNAP-TIL product comprising, on average, 96% CD3+ cells, with a favorable mixture of 75% effector and 23% central memory cells. In ex vivo models, SNAP-TILs demonstrated greater efficacy and selectivity in immune infiltration compared to TILs expanded solely by the rapid expansion protocol. Critically, SNAP-TILs exhibited robust reactivity in both highly and poorly immunogenic tumors. > In patient-derived xenograft models, SNAP-TIL therapy achieved 70% tumor growth inhibition in melanoma and 50% tumor growth inhibition in pancreatic cancer models. This indicates the platform's ability to generate potent, tumor-specific T-cell responses across different tumor types, addressing a key limitation of conventional TIL approaches.