1676P Active immunization with a multi-peptide B cell vaccine, targeting trastuzumab and pertuzumab binding sites, prevents the formation of HER-2/neu expressing lung metastases

Abstract

The passive application of Trastuzumab and Pertuzumab has demonstrated remarkable success in the clinical outcome of patients with Her-2/neu positive metastatic breast cancer. However, active immunization with mimotope/B cell epitope-based vaccines can induce the production of the corresponding mAbs by the patient’s immune system. We have developed a B cell peptide-based Her-2/neu vaccine (HerVaxx) comprising Trastuzumab’s binding site. In clinical settings, the vaccine has been shown to reduce primary tumor growth by inducing polyclonal anti-tumor immune responses and immunological memory. The vaccine was also shown to result in loss of Her-2/neu expression, a phenomenon similarly observed in the clinic after treatment with Trastuzumab. Applying a Her-2/neu lung metastasis mouse model, here we tested a multi-peptide B cell vaccine containing HerVaxx and a mimotope of Pertuzumab for the prevention of lung metastases formation and investigated the loss of Her-2/neu expression. Mice were vaccinated with the multi-peptide vaccine, tail-vein injected with mammary carcinoma cells expressing human Her-2/neu, and histological evaluations of the mice lungs were carried out. A significantly reduced lung metastasis formation by active immunization with either the mimotope of Pertuzumab, HerVaxx, or the combination of both, was observed and associated with decreased lung weights and increased CD4+ and CD8+ T cells infiltration. Markedly, along with the overall reduction of lung weights and Her-2 positive metastases, the formation of Her-2/neu-negative tumors but with increased PD-L1 expression was observed. Our data might result in a multi-peptide B cell Her-2/neu vaccine serving as a secondary intervention in adjuvant settings to prevent tumor recurrence and spread. Furthermore, the loss of Her-2/neu expression suggests a combination therapy involving an anti-PD-L1 immune checkpoint inhibitor or an active immunization with a mimotope from PD-L1. Such combination therapy to alternately target Her-2/neu and PD-L1 might be adapted to the stage and progression phase of the disease and result in the remission of the metastases.