HER-2 therapeutic vaccine is not hampered by concurrent HER-2 monoclonal antibody

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Abstract
ES2B-C001 represents a new generation of vaccines based on virus-like particles (VLP) that display the full extracellular domain of HER-2 and has now entered clinical development. ES2B-C001 elicited strong anti-HER-2 antibody responses that cured human HER-2 transgenic tumors and metastases in mice. Early vaccine trials may include patients who are still receiving anti-HER-2 monoclonal antibody (MAb) therapy, a clinical scenario that has not typically been addressed in preclinical studies. To evaluate whether the concurrent administration of 4D5 anti-HER-2 MAb affects the immunogenicity or the therapeutic efficacy of ES2B-C001, we administered concurrent treatments to tumor-free or to human HER-2 transgenic mammary carcinoma-bearing mice. In tumor-free mice, 4D5 treatment did not hamper either ES2B-C001 activity, which induced a strong anti-HER-2 IgG production, or T cell responses. In tumor-bearing mice, the therapeutic efficacy of ES2B-C001 was not compromised by 4D5, resulting in 13/20 long-term tumor-free mice with ES2B-C001 alone, versus 15/20 with the combined treatment. ES2B-C001 elicited robust HER-2-specific antibody responses, reaching concentrations in the milligram/mL range and persisting for >6 months post-treatments, regardless of prior 4D5 administration. These findings indicate that co-administration of an anti-HER-2 MAb does not impair the efficacy of ES2B-C001, supporting the feasibility of vaccinating patients undergoing trastuzumab therapy.

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