Dr. Sangeeta Bhaskar

Summary of Research:

Protective Efficacy of MIP in Animal Models of Tuberculosis
Whole bacterial vaccines rely on multiple antigens and built-in-adjuvanticity. Mycobacterial strains which share cross-reactive antigens with M.tuberculosis are  being considered as alternatives to M.bovis for vaccine use. Mycobacterium indicus pranii (MIP) shares antigens with M.tuberculosis and initial studies had shown that vaccination with killed MIP induces protection against tuberculosis. Hence, we further studied the protective potential of MIPand the underlying immune responses. This study aims to investigate the protective efficacy of MIP immunisation in live or killed form, through parenteral route as well as by aerosol immunization, against subsequent infection with M.tuberculosis in animal models. Study of immune response to M.tuberculosis in animals immunised with MIP. These responses are compared with those generated in BCG immunised mice.

The extended course of chemotherapy often results in poor compliance and the emergence of drug resistant strains. Therefore, improved therapeutic strategies are needed. Immunotherapy can boost protective immune responses and could contribute to the effective management of the disease when combined with chemotherapy. We sought to investigate whether MIP could be used as an adjunct to standard chemotherapy in guinea pig model of tuberculosis. The efficacy of MIP was evaluated when given by aerosol or parenteral route at  sub acute or chronic stage of tuberculosis infection.

Immunotherapeutic Potential of MIP and the Underlying Mechanisms in Mouse Tumor Model

Role of the immune system in protecting the host from cancer is well established. The generation of antitumor immunity is often difficult in the tumor-bearing host because of various negative regulatory mechanisms. Activation of Innate and Th1 type immune response is important to overcome immunosuppression in the tumor-bearing hosts. There were indications from different clinical studies that MIP may be useful as an immunomodulatory adjunct in some cancers. In animal model of tuberculosis we had found that MIP induces Th1 type response, which is also important for antitumor activity. Hence, we sought to analyse the immunotherapeutic potential of MIP in mouse tumor model and the underlying mechanisms for its antitumor activity. Study of MIPas an adjunct to chemotherapy in combination with commercial anti cancer drug formulation in tumor bearing mice and simultaneous study of mechanism of MIP mediated host immune activation.

Combined chemo-immunotherapy strategies to combat cancer

It is well established that tumor suppresses the anticancer immune response at its local microenvironment to facilitate its growth, leading to cancer progression and metastasis. Immunotherapy, on the other hand, stimulates the immune system and helps to induce an effective anti-tumor response. Combined chemo-immunotherapy has multi faceted advantages. Chemotherapy induced cell death can enhance cross-priming of immune cells by providing them with important cancer specific antigens, thereby increasing the antitumor T cell response.

The prime objective of this study is to develop a combined chemo-immunotherapeutic formulations which could directly kill cancer cells as well as activate the suppressed tumor microenvironment to promote killing of tumor cells. Paclitaxel (PTX) and SP-LPS (non-toxic derivative of lipopolysaccharide) were selected as anti-cancer drug and immunostimulant respectively. We prepared a chemo-immunotherapeutic compound by conjugating a chemotherapeutic drug with an immune stimulant and also prepared nanoparticles co-encasulating both and their anticancer activity was evaluated. Further work with other polymers having macrophage stimulating property and antitumor activity is planned.