Evaluating the Potential of Chineric IL - 15 on Re - Activation of CD8+ T- Cells in Tumor Model

Abstract

Our immune system has an inherent function to locate and eliminate tumors; however tumors have evolved mechanisms to evade immune surveillance with the help of several immunomodulatory pathways rendering immune cells deactivated. One of the most promising approaches in tackling cancer is by augmenting immune responses with the help of cytokines which facilitate reactivation of immune cells and help regaining the ability to eliminate malignancies. IL-15 is one such immunotherapeutic cytokine which is first in the list among 12 immunotherapeutic drugs released by the National Cancer institute, NIH, USA. Chimeric fusion proteins have been reported to exhibit anti-tumor activity in several tumor models. Native IL has limitations like short half-life, poor bioavailability and toxicity which was overcome by developing a fusion protein having specific mutation incorporated IL-15 fuses with Fc region of IgG/2a immunoglobulin making it an ideal molecule for cytokine therapy. An Indian patent was filed for this invention and has been published (Indian Patent Application No. 201721010096A). In this study we examined the activation status of T lymphocytes and anti-tumor activity of this Chimeric IL-15 in tumor bearing mice when administered via IP(intra-peritoneal) and IV(intra-venous routes). Our results show presence of IL-15 functional domains in the fusion protein which is essentially required for the biological activity. Current study also successfully shows that Chimeric IL-15 increases CD8+ T cell infiltration and an increase in proportion of activated CD8+ T cells in tumor microenvironment making it a suitable immunotherapeutic candidate for further studies on tumor models.