Rao H. Prabhala, PhD

Immune Cell Dysfunction and Immunotherapy in Multiple Myeloma

The major focus of our research has been the identification of immune cell dysfunction, particularly in the CD4+ population of multiple myeloma and the development of molecular therapeutic strategies, including immunotherapy.

We are working to develop immune-based therapies in our laboratory for clinical use.  We are the first group to show that regulatory T cells are dysfunctional in myeloma, which provided the rationale for clinical trials in myeloma patients.  Then, we started a study on Th17 cells and associated pro-inflammatory cytokines; a number of critical observations were made allowing for a better understand of myeloma pathogenesis.  We have shown that there are increased Th17 cells and associated cytokines in myeloma. These cytokines, particularly IL-17, promote myeloma growth for both in vitro and in vivo studies.

Based on our pre-clinical results, we are developing clinical trials to evaluate targeted strategies for myeloma. In particular, we are in the process of evaluating the efficacy of the anti-IL-17 human antibodies either alone or in combination with chemotherapeutic agents.  Additionally, we are evaluating myeloma-specific antigens to generate chimeric antigen receptor-based T cell therapies.         

Another area of research in our laboratory is the evaluation of B cell-subsets in myeloma.  It has been well-documented that normal immunoglobulin levels are lower in myeloma; myeloma patients are unable to develop robust antibody responses, following Hepatitis B surface antigen vaccinations.  These results indicate that the B cell-compartment does not function as effectively, in comparison with healthy donors. 

The long-term goal of our research efforts is to develop combinational therapeutic approaches to myeloma treatment using immunotherapy as an anchor.