ArticleTranslational lung cancer research2025
Combination of racotumomab immunotherapy with programmed death-1 blockade in a preclinical model of non-small cell lung cancer.
Article in Translational lung cancer research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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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.
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