Combinational Pulsing of TAAs Enforces Dendritic Cell-Based Immunotherapy through T-Cell Proliferation and Interferon-γ Secretion in LLC1 Mouse Model.

Simple Summary: Despite the proven efficacy and confirmed safety of dendritic cell therapy, the limited response against cancer remains a challenge. This study aimed to investigate the potential of combinational tumor-associated antigens (TAAs) pulsing to enhance the antigen-presenting ability of dendritic cells. TAAs-pulsed DCs demonstrated anti-cancer capabilities, including tumor growth suppression, increased proliferation of splenic T cells, and elevated IFN-γ secretion. While the combinational pulsing approach shows promise in addressing the limitations of dendritic cell therapies, additional research is required to explore diverse combinations of TAAs for potential therapeutic applications. NSCLC, the most common type of lung cancer, is often diagnosed late due to minimal early symptoms. Its high risk of recurrence or metastasis post-chemotherapy makes DC-based immunotherapy a promising strategy, offering targeted cancer destruction, low side effects, memory formation, and overcoming the immune evasive ability of cancers. However, the limited response to DCs pulsed with single antigens remains a significant challenge. To overcome this, we enhanced DC antigen presentation by pulsing with TAAs. Our study focused on enhancing DC-mediated immune response specificity and intensity by combinatorial pulsing of TAAs, selected for their prevalence in NSCLC. We selected four types of TAAs expressed in NSCLC and pulsed DCs with the optimal combination. Next, we administered TAAs-pulsed DCs into the LLC1 mouse model to evaluate their anti-tumor efficacy. Our results showed that TAAs-pulsed DCs significantly reduced tumor size and promoted apoptosis in tumor tissue. Moreover, TAAs-pulsed DCs significantly increased total T cells in the spleen compared to the unpulsed DCs. Additionally, in vitro stimulation of splenocytes from the TAAs-pulsed DCs showed notable T-cell proliferation and increased IFN-γ secretion. Our findings demonstrate the potential of multiple TAA pulsing to enhance the antigen-presenting capacity of DCs, thereby strengthening the immune response against tumors. [ABSTRACT FROM AUTHOR]