Study of Effect of Human Chimeric II-15 on T-Cell Activation

Abstract

Cancer is one of the leading causes of death in the human population after heart disease. Despite the availability of various modalities, the gravity of cancer mortality and morbidity increasing. The immune system plays an important role in the regression of cancer. Various Immunotherapeutic approach may help to overcome the burden within the tumor microenvironment. Among the various immunotherapeutic approach Cytokine-based immunotherapy has the potential to be an effective treatment option for certain types of cancer. Cytokines are proteins that help in regulation of immune responses, including the activation and proliferation of T cells and natural killer (NK) cells. Interleukin-15 (IL-15) is a cytokine that plays an important role in the immune system's response against the cancer. IL-15 activates and expands a specific type of immune cell called NK cells, which can recognize and kill cancer cells. IL-15 can also enhance the activity of other immune cells, such as T cells and dendritic cells, which can also contribute to the immune response against cancer. Previous studies data demonstrating the effectiveness and limitations of Cytokine-based immunotherapy analogs given as an exogenous immuno-oncology agent. To resolve the problem of low stability and serum half-life, earlier our lab has made modified chimeric Human IL-15 protein covalently linked with mouse IgG2 having high stability and longer half-life. In vitro and In vivo study will give an idea of the biological activity of chimeric huIL-15 signaling and CD8+ T cell response in favour of activation and memory generation. To address our objective, we analyses the T-cell activation and secretion of INF-γ in the human HLA-A*02 and HLA-B*35:03 PBMCs with or without stimulation of ESAT- 6 and PRAME peptide respectively at different concentration using flow cytometry. Our data analyses demonstrate that the peptide stimulated PBMCs are secreting more IFN-γ compare to non-stimulated cells. Hence, we can conclude that the peptides designed for specific HLA were effectively activating the PBMCs. In future PBMCs will be stimulated along with or without Peptide and chimeric huIL-15 or in the presence of both and it will be looked for T-cell activation and secretion of INF-γ