The Society for Immunotherapy of Cancer, SITC, selected Gabrielle Romain, post-doctoral research fellow in the UH Cullen College of Engineering, to present her research on cancer immunotherapy at its 30th anniversary annual meeting. With an approximate $750 travel grant, she plans to attend the conference in National Harbor, Maryland, in November.
Chemotherapy, radiation and surgery remain the most pervasive treatment options for cancer patients, but immunotherapy, which harnesses the immune system to fight cancer, is showing promise in small clinical trials. One such therapy is adoptive cell transfer, ACT, which involves genetic modification of T cells, a type of immune cell, to produce surface chimeric antigen receptors, or CARs, that recognize proteins on surfaces of antigens. Billions of these CAR T cells are grown in labs and infused into patients’ bodies where they multiply and attack cancerous tumors.
CAR T cells have demonstrated clinical promise for combating even late-stage cancerous tumors resistant to all or most other types of treatments, but therapy outcomes remain somewhat unpredictable. Therefore, new approaches are necessary to assess potential for the treatment of cancers with immunotherapies, and Timelapse Imaging Microscopy In Nanowell Grids, or TIMING, which Romain and her colleagues developed, is showing promise.
Using their novel single-cell assay, Romain compared the efficacy of two different CD19-specific CAR constructs by tracking their interactions with tumor cells in vitro. CAR T cells rendered specifically for CD19 have demonstrated significant antitumor properties in patients with CD19 chronic lymphocytic leukemia, CLL, and acute lymphoblastic leukemia, ALL. Lymphomas have also responded positively to CD19 CAR T cells.
While discernible differences were not observed in populations of cells, Romain determined with TIMING that significantly more CAR T cells bearing CD8a receptor components participated in serial killing of NALM6 tumor cells than those with IgG4 components. A mouse model confirmed the superiority of CAR T cells containing CD8a in controlling the disease. Navin Varadarajan, assistant professor of chemical and biomolecular engineering at UH Cullen College, and Laurence Cooper, associate professor of pediatrics at the University of Texas M.D. Anderson Cancer Center, were lead investigators on the study.
“In aggregate, these results demonstrate the utility of TIMING single cell methodology in uncovering not only the dynamic profile of T-cell behavior but in also uncovering the phenotypic biomarkers of CAR T cells with superior functional efficacy,” Romain wrote in her abstract.