Abstract
Background:
Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related death. Treatment options include surgery, chemotherapy, radiotherapy, and immunotherapy, such as anti-programmed death-1 (PD-1) monoclonal antibody (mAb) pembrolizumab. Combining anti-PD-1 therapy with other active immunotherapies is an interesting option for improving patient outcomes. Racotumomab, an anti-idiotype mAb used as switch maintenance therapy in advanced NSCLC, enhances immune responses against N-glycolylneuraminic acid (NeuGc)-containing neoantigens. This study aims to assess the antitumor effects of an anti-murine PD-1 mAb in combination with racotumomab immunotherapy in a preclinical mouse model of NSCLC.
Methods:
In the present study, we assessed the antitumor effects of an anti-murine PD-1 mAb in combination with racotumomab immunotherapy in a Lewis lung carcinoma (LLC) mouse model, employing two treatment schedules. Syngeneic C57BL/6 mice were injected intravenously with LLC cells and treated with 1-2 doses of anti-PD-1 mAb [200 µg, intraperitoneal (IP)] and/or three weekly doses of racotumomab [200 µg, subcutaneous (SC)].
Results:
Although concurrent treatment did not improve the effect of monotherapies, sequential treatment with anti-PD-1 followed by racotumomab immunization produced a significantly higher reduction in lung nodule formation. Additionally, we demonstrated a significant association between dietary incorporation of exogenous NeuGc and the antitumor activity of racotumomab using a humanized NeuGc-negative mouse model that lacks the key enzyme necessary for NeuGc synthesis.
Conclusions:
Our preclinical data strongly support the efficacy of a sequential combination of PD-1 checkpoint blockade therapy and active vaccine immunotherapy racotumomab in the treatment of advanced NSCLC.