Research themes
- Development of new chimeric antigen receptors for human disease
- Potential mechanisms of resistance and toxicity
- Next-generation production systems for cellular therapies
Cell therapy breakthroughs and innovations
The Davila Lab is centered around chimeric antigen receptor (CAR) T-cell therapy and the implications associated with it. Our scope of research stretches from preclinical to clinical. We utilize multiple techniques for both in vitro and in vivo experiments, using streamlined technologies that allow for unique and precise data collection. Traditional methods are also integrated within our work such as flow cytometry and multiple different molecular assays.
Our in vivo work includes different immune competent and immune deficient tumor models. These models aid in demonstrating the importance and interplay between the innate and adaptive immune systems while studying CAR T-cell therapies, as well as the tumor microenvironment.
Understanding CAR T-cell toxicities
During the 2022 American Society of Hematology annual meeting, Dr. Davila and predoctoral trainee Payal Goala, MS, BS, presented research findings that address two significant toxicities associated with CAR T-cell therapy.
While breakthroughs in cellular therapy treatment have led to major improvements in survival for patients with B-cell acute lymphoblastic leukemia (B-ALL), recent investigation has highlighted the negative impact of CAR T-cell therapy related adverse events, particularly cytokine release syndrome and cytopenia such as neutropenia.
To establish a model that has the capability to study both cytokine release syndrome and neutropenia, the Davila Lab team examined the role of IL-2Rα in inducing CAR T-cell therapy related toxicities.
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Research brief: Predicting CAR T-cell therapy outcomes in lymphoma patients
An international team led by Dr. Davila developed and validated a new approach for assessing and responding to elevated risk – using two common blood tests.
CAR T-cell therapy resistance in B-cell malignancies
A podium talk at the 2023 Tandem Meetings featured the Davila Lab’s work in identifying the pathways by which macrophages kill and suppress CD19-targeted CAR T cells, resulting in poor outcomes among patients with B-cell malignancies who receive CAR T-cell therapy.
Using patient samples, we identified gene signatures and cell signatures showing that the lymphoid tissue in those patients contained high numbers of myeloid cells, which originate in the bone marrow and can develop into various types of adult blood cells, including macrophages.
We then developed assays of CD19-targeted CAR T cells, tumors and macrophages, and cultured them together — and discovered that certain types of macrophages are capable of killing CAR T cells.
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Department of Immunology
Roswell Park Comprehensive Cancer Center
Elm and Carlton Streets
Buffalo, NY 14263