Several advancements are made in the field of immunotherapy for enabling an effective cure for cancer. Treatments are being approached with multipronged approach with combination therapies as well as by gene therapy. Cancer incidence however progressing further mainly due to the changes in lifestyle. Epidemiological surveys indicate that cancer incidence is being more predominant in females; in particularly breast cancer is the most common diseases throughout world. However, the treatments attempted to deal with breast cancers especially triple negative cancer hasn't shown considerable success. NK cell therapy has shown some progress in initial stages of breast cancer, not in metastatic breast cancer. This is due to inefficient NK cells anti-tumor response. The anti-tumor response of NK cell is varied as based on exposed to a range of cytokines and/or mitogen.
We have evaluated the anti-tumor immune response of NK cell by using IL2 combination with less virulent Streptococcus pyogenes of human origin (OK432, Picibanil, manufactured in Japan). Cell doubling time, Immunophenotyping, mRNA expression and cytotoxicity of NK cells against MDA-MB-231 breast cancer cell line were performed and compared between with and without OK432.
Our results show that there was no difference in terms of NK cell proliferation between with and without OK432 expansion and an average cell fold was increased to mean of 200 ± 3.5. However, the surface marker of CD56+ and CD16+ were remarkably expressed on NK cells cultured with OK432 (85.5 ± 0.9, 60 ± 0.7) than the cells cultured without OK432 (65.5 ± 0.9, 50 ± 0.7). Subsequently, the gene expression pattern of Perforin and NKG2D was significantly increased in cells cultured with OK432 as compared to without OK432. Cytotoxicity analysis revealed that NK cells cultured with OK432 lysed the target cancer cells faster than the cells cultured without OK432 in time and dose (E:T ratio) dependent manner.
Overall our results suggested that OK432 has a vital role to play in NK cell augmentation for effective cell-mediated lysis.