Associate Professor, Medicine: Hematology and Oncology
- MS, Biological Sciences, Bhopal University
- PhD, , All India Institute of Medical Sciences
- Postdoc, , Free University of Berlin
Dr. Thakur's research activities are focused on 1) developing new and innovative therapeutic approaches to enhance clinical and anti-tumor immune responses; 2) developing novel strategies to attenuate the immune suppressive cellular and humoral factors.
Our tumor targeting strategy is based on arming activated T cells with low concentrations of bispecific antibodies to bridge the effector T cells with targets, resulting in tumor cell lysis, T helper type 1 (Th1) cytokine/chemokine release, and induction of long-term immune responses without causing the severe cytokine release syndrome. We have shown enhanced tumor cell killing by bispecific antibody armed T cells in the presence of the Th1 cytokine-enriched microenvironment as well as reduced myeloid-derived suppressor cells (MDSC) and T regulatory cells (Treg). Our working hypothesis is that infusions of T cells armed with bispecific antibodies in cancer patients not only provide immediate tumor cell killing but also modify the tumor microenvironment through the release of Th1 cytokines and chemokines. Tumor cell lysis by bispecific antibody armed T cells may create fertile ground for in situ immunization through the inhibition of Tregs and MDSC populations by shifting Th1/Th2 cytokine ratio, antigen/epitope spreading through recruitment and activation of endogenous APC and other immune cells. We have also designed a novel co-culture system for immune correlative studies which provides a powerful tool for interrogating the ability of normal and patient PBMC to produce specific anti-tumor antibodies. More importantly, it is a sensitive probe for monitoring the humoral immune responses and may help identify and dissect the regulatory interactions of T-cells and B-cells.