Phenotyping T Cells in Tumor-Microenvironment and Studying The Effect of Plasmid Chimeric IL-15 in Prophylactic Vaccine Approach

Abstract

Cytokines are one of the key molecules that plays a crucial role to regulate the innate and adaptive immunity and inflammatory responses. Tumor microenvironment has its own entity that suppress the host immunity and escape from immune surveillance. A host defense mechanism cells that assumed to detect, regress or eliminate tumor, favors the tumor growth. IL-15 is a cytokine that is pleotropic in nature and activates T cell response. It also helps into the activation and maintenance of effector memory and central memory T cell. NK cells and T cells are activated by IL-15, which regulates IFN-γ production, that in line activates other immune cells. Moreover, it encourages the production of anti-apoptotic proteins, which in turn prolongs the vital immune cell’s ability to fight against antigens. Certain limitations like poor bio-availability, short half-life, increased risk of NK cells mediated toxicity, and soluble nature limits the use of IL-15 as cytokine therapy. Limitations were eliminated by ‘Chimeric IL-15’, a patented molecule of Institute of Science, Nirma University. IL-15 was used as an adjuvant in various vaccine strategies for TB, Influenza, Malaria and HIV, etc.; due to its potent role in activating good T cell response. On the basis of previous findings, we assumed that ch.IL-15 should mount a good anti-tumor T cell response and generate memory response for the same. In this study we focused on two approaches by which how we can use ch.IL-15 to treat or eliminate cancer, one is preventive DNA-vaccine approach and another is cytokine therapeutic approach. Study demonstrates the use of plasmid vector pcDNA3.1 construct with ch.IL-15 conjugated gene in to it. 2 dosages of this plasmid at the interval of 14 days were administered to healthy mice, followed by tumor-cell challenge at 28th day to check if pre-immunization by ch.IL-15 plasmid construct, helps to delay the tumor growth compared to control group or no tumor growth. Experimental data showed that ch.IL-15 plasmid construct dosing as pre-vaccination purpose proved successful to stop the tumor growth and related good prognosis of cancer models in-vivo. Another approach involves the use of plasmid construct of ch.IL-15 as therapeutic approach to treat (regress/eliminate) tumor in B16F10-OVA melanoma C57 mice model.