National Cancer Institute 5R01CA262629-05

Personalized Adoptive T-cell Therapy for AML

This award funds a project to develop a personalized adoptive T-cell therapy for Acute Myeloid Leukemia (AML) using a novel vaccine-mediated T cell expansion strategy, including a Phase I clinical trial to evaluate therapy efficacy and immune response.

Description

The project aims to develop a personalized adoptive T-cell therapy for Acute Myeloid Leukemia (AML) by designing a novel combination strategy for vaccine-mediated ex vivo T cell expansion. The approach promotes the expansion of central memory T cells, enhances activation and expansion of dominant clones, and reverses immunosuppressive mediators via TGFβ inhibition. Patient-specific DC/AML fusions will be used to interrogate T cell clones targeting neoantigens. The study will translate preclinical findings into a Phase I clinical trial, examining the correlation between T cell product characteristics and clinical outcomes such as toxicity, activation, expansion, persistence, and relapse prevention. The project builds on prior success with a personalized cancer vaccine platform that fused patient-derived tumor cells with autologous dendritic cells, generating leukemia-specific T cells capable of capturing tumor heterogeneity. Transcriptome analysis identified TGF-β as a negative regulator of immune response, providing a rationale for TGFβ targeting to enhance vaccine efficacy. Functional characterization of T cell products will include targeting of shared and neo-antigen targets, oligoclonal expansion, and markers of activation, exhaustion, and migration. The clinical component involves a Phase I trial where AML patients in remission will receive adoptive T-cell therapy stimulated by the vaccine, aiming to improve long-term remission and immune memory.

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