Davila Lab Research

Cell therapy breakthroughs and innovations

The Davila Lab is centered around chimeric antigen receptor (CAR) T-cell therapy, from preclinical development to clinical translation. Our research focuses on advancing our understanding of T cell function, tumor targeting, and mechanisms of resistance. We utilize sophisticated in vitro and in vivo techniques including single-cell transcriptomics and CRISPR-based gene editing, integrated with traditional methods like flow cytometry, cytokine profiling, and molecular assays. Our in vivo work includes both immune competent and immune deficient tumor models to more accurately capture the complexity of human cancer. These models allow us to demonstrate how the innate and adaptive immune systems interact during CAR T-cell therapy and to evaluate how the tumor microenvironment influences therapeutic efficacy, persistence, and resistance.

Engineering CAR T cells to resist immunosuppression in the tumor microenvironment

The Davila Lab has developed TGFβR2 knockout (TGFβR2KO) CAR T cells, designed to resist suppression in the tumor microenvironment. Building on preclinical work demonstrating enhanced persistence, cytokine production, and tumor control in xenograft models of hepatocellular carcinoma, autologous CAR T cells engineered with CRISPR/Cas9 to disrupt TGFβR2 and target GPC3 received Investigational New Drug (IND) approval by the FDA in 2025. A first-in-human Phase I clinical trial evaluating the safety and early efficacy these CAR T cells in patients with relapsed or refractory hepatocellular carcinoma is now open at Roswell Park Comprehensive Cancer Center. This represents one of the first clinical trials testing a CRISPR-edited CAR T therapy for solid tumors, marking a significant step toward overcoming resistance mechanisms that have limited the impact of CAR T cells beyond hematologic cancers.

Targeting CD83 to overcome CD19 antigen loss in B cell malignancies

A major focus of research in the Davila Lab is resistance to CAR T cell therapy, and we have recently addressed this challenge by generating preclinical data to support an innovative clinical trial targeting CD83 in acute myeloid leukemia (AML). Building on successes with CD19-directed CAR T therapies for B cell malignancies, which face limitations like antigen loss and prolonged B cell aplasia, we demonstrated that CD83 is a promising alternative target. We showed that CD83 is robustly expressed in various B cell malignancies and not in healthy circulating B cells. Importantly, CD83-targeted CAR T cells maintained efficacy in vitro and in vivo even against tumors that had lost CD19 expression or had been previously exposed to CD19 CAR T cell therapy, suggesting a powerful avenue for treating relapsed disease. This work underpinned the development of the current phase I clinical trial at Roswell Park, which will test CD83 CAR T cells in patients with relapsed or refractory AML. By targeting a novel antigen with potentially reduced off-tumor toxicity, this trial exemplifies a major improvement in CAR T cell therapy to address pressing clinical challenges.

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Department of Immunology
Roswell Park Comprehensive Cancer Center
Elm and Carlton Streets
Buffalo, NY 14263