SITC 2021: How Genetic Reprogramming of Merkel Cell Carcinoma May Impact MHC-I Expression and Immune Response
Posted: Friday, December 3, 2021
Jordan Green, PhD, of Johns Hopkins University, Baltimore, Maryland, and colleagues attempted to genetically reprogram cells of Merkel cell carcinoma to express their own immunostimulatory cytokines and co-stimulatory molecules. Their findings, presented during the 2021 Society for Immunotherapy of Cancer (SITC) Annual Meeting (Abstract 222), concluded that signal 2/3 nanoparticles have the potential to reprogram these cells, achieving immune response and increased major histocompatibility complex (MHC)-I expression.
Biodegradable poly nanoparticles were used to co-deliver plasmids that encoded a signal 2 (4-1BBL) and two signal 3 molecules (IL-12 and IFN-g) into cancer cells. In vitro evaluation used two patient-derived cell lines of Merkel cell carcinoma that had low baseline expression of MHC-I: MCC13 and UISO. In vivo evaluation was performed by implanting subcutaneous melanoma tumors into C57BL/6J mice and injecting nanoparticles into the tumor.
Compared with controls, MHC-I expression was increased 1.6- and 5.0-fold in MCC13 and UISO cell lines, respectively; MHC-II expression was increased 1.6- and 6.3-fold. When co-cultured with human peripheral blood mononuclear cells, signal 2/3 particles demonstrated significantly reduced viability of Merkel cell carcinoma (10.6% and 1.6%) as well as increased leukocyte proliferation.
When co-cultured with human natural killer cells, however, natural killer cell expansion appeared to increase 355-fold with these particles compared with controls, demonstrating a 2.5% cell viability among the MCC13 cell line. Additionally, an increased expression of MHC-I and MHC-II was observed with signal 2/3 nanoparticles compared with control nanoparticles. Notably, signal 2/3 nanoparticles in combination with anti–PD-1 treatment appeared to demonstrate improved overall survival compared with treatment with control nanoparticles (P = .001).
Disclosure: No disclosure information was provided.
