Jones Seminar: Nanoscale Approaches for Therapeutic Immune Modulation

Ashish Kulkarni, Harvard Medical School and Brigham and Women’s Hospital

Friday, March 3, 2017, 3:30–4:30pm

Rm. 100 (Spanos Auditorium), Cummings Hall

Immunotherapy has emerged as the new paradigm in the treatment of cancer. However, durable responses are observed in a limited patient population primarily due to strong immunosuppressive tumor microenvironment that hampers efficient anti-tumor immune responses. For example, tumors are heavily infiltrated with tumor -associated macrophages, which facilitate tumor progression, confer resistance to chemotherapy, and directly and indirectly mount an immune suppressive effect on T cells. I will present a nanotechnology-based approach, called supramolecular nanotherapeutics, which can be used to focally modulate the tumor immune contexture towards the immune responsive mode with minimal systemic side effects. We have observed that supramolecular nanotherapeutics can exert a sustained tumor regression in immunocompetent syngeneic murine models of breast cancer and melanoma by efficiently converting immunosuppressive tumor macrophages to effector macrophages. 

Secondly, accurate monitoring of clinical efficacy is challenging since the response does not always follow conventional response assessment criteria due to delayed and variable kinetics in immunotherapy responses. Also, current morphological or functional imaging techniques lack the sensitivity and specificity to enable early response assessment. Furthermore, results from immune biomarker and immune response assays are highly variable and often non-reproducible. I will show that a real-time imaging of immunotherapy response could be achieved by biologically-inspired engineering of a self-reporting nanotheranostics that can enable spatiotemporal delivery of an immunotherapy drug and drug function-activatable imaging agent. The development of these nanotechnology-based platform technologies that can not only improve immunotherapy response but also monitor its efficacy early on can have a significant impact on the outcome as well as quality of life of patients.

About the Speaker

Dr. Ashish Kulkarni is an Instructor of Medicine at Harvard Medical School and Associate Bioengineer at Brigham and Women’s Hospital. He obtained his B Tech in chemical technology from Institute of Chemical Technology, University of Mumbai and a PhD in Chemistry from University of Cincinnati, Ohio. During his PhD, he worked on the design and development of biologically-inspired and chemically-defined synthetic glycans for diagnostic and therapeutic applications. After his PhD, he joined Harvard Medical School and MIT as a postdoctoral fellow with Prof. Shiladitya Sengupta. In Prof. Sengupta laboratory, his research efforts were focused on the development of structure-activity relationship-inspired nanomedicine for cancer therapy.

As an independent faculty at Harvard, he is working on the development of platform technologies for immunotherapy applications. His work is published in very high impact journals and also gathered a lot of attention and featured in several science media outlets. He is a recipient of the Hearst Foundation Young Investigator Award, Dana-Farber/Harvard Cancer Center Career Development Award, American Association of Cancer Research (AACR) Scholar-in-training Award, American Society of Pharmacology and Experimental Therapeutics (ASPET) Young Scientist Award and Junior Faculty Mentor Award. 

For more information, contact Marge Heggison at marge.heggison@dartmouth.edu.