CELL INTELLIGENCE · 肿瘤细胞治疗研究

The discovery of tumor-associated antigens has been a significant milestone for cancer therapy as the current conventional therapies (radiotherapy, chemotherapy) were found to be insufficient in terms of cancer treatment. Human epidermal growth factor receptor (HER2) is a tumor-associated antigen, aberrantly found in various cancers, including breast cancer.

Today, most treatment strategies are skewed toward combination therapies rather than monotherapies, as they have been found primarily ineffective due to patients' resistance mechanisms. A combination of multiple therapeutic approaches (passive/active immunotherapy, conventional therapies) was found to be more effective in the clinic.

This study investigated various vaccine combinations against the 4 T1-HER2 xenograft model of Balb/c mice. Eight different groups of vaccine formulations were tested to find the best synergistic combination, including combinations of BM-DC-based vaccine, peptide-based vaccine, anti-PD-L1, Doxorubicin, and QS-21 adjuvant. Triple combination groups of immunotherapies exerted better activities in terms of tumor dimensions as Doxorubicin+BM-DC-HER2/Neu + QS-21 + anti-PD-L1 and Doxorubicin+HER2/Neu + QS-21 + anti-PD-L1 groups significantly decreased tumor dimensions.

Similar groups also demonstrated a better stimulation of lymphocytes and IFN-γ cytokine in the flow cytometry study, inducing a HER2/Neu-specific antibody response in ELISA studies. Doxorubicin+BM-DC-HER2/Neu + QS-21 + anti-PD-L1 combination demonstrated significantly higher specific cytotoxicity in lactate dehydrogenase data, as well as the CD4+ and CD8+ responses in the immunohistochemical study.

In conclusion, these data indicated that the Doxorubicin+BM-DC + HER2/Neu + QS-21 + anti-PD-L1 vaccine combination synergistically generated a promising activity in terms of tumor dimension and immune response stimulation against the HER2 overexpressing breast cancer model in mice.