Clinical and Experimental Vaccine Research

The Korean Vaccine Society (대한백신학회)
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Formulation of an ovarian cancer vaccine with the squalene-based AddaVax adjuvant inhibits the growth of murine epithelial ovarian carcinomas

  • Suparna Mazumder (Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic) ;
  • Valerie Swank (Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic) ;
  • Nina Dvorina (Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic) ;
  • Justin M. Johnson (Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic) ;
  • Vincent K. Tuohy (Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic)
  • Received : 2022.03.24
  • Accepted : 2022.05.10
  • Published : 2022.05.31
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Abstract

Purpose: Epithelial ovarian carcinoma (EOC) is the most lethal of all human gynecologic malignancies. We previously reported that vaccination of female mice with the extracellular domain of anti-Müllerian hormone receptor II (AMHR2-ED) in complete Freund's adjuvant (CFA) generates AMHR2-ED specific immunoglobulin G (IgG) that provides prevention and therapy against murine EOCs. Although CFA is the "gold standard" adjuvant in animal studies, it is not approved for human use because it often induces painful granulomas and abscesses. Thus, the objective of this study is to identify an alternative adjuvant to CFA for use in our ovarian cancer vaccine clinical trials. Materials and Methods: Because it has been used successfully without serious adverse effects in numerous human clinical trials, we selected the IgG-inducing squalene-based adjuvant, AddaVaxTM, for evaluation of its ability to facilitate vaccine-induced prevention and treatment of EOC in mice. To this end, we immunized female C57BL/6 mice with recombinant mouse AMHR2-ED emulsified with either AddaVax or CFA as adjuvant and compared the results. Results: We found that formulation of the AMHR2-ED vaccine with AddaVax adjuvant induced high serum titers of IgG and significant inhibition of EOC growth with significantly enhanced overall survival of mice using both prevention and therapeutic protocols. These results were compared favorably with results obtained using CFA as an adjuvant in the AMHR2-ED vaccine. Conclusion: Our data indicate that the AMHR2-ED vaccine formulated with AddaVax may be used in human clinical trials and thereby serve as a novel and effective way to control human EOC.

Keywords

Acknowledgement

This study was funded in part from a Cleveland Clinic Velosano Award (SM), a Cleveland Clinic Center of Excellence Award (VKT), a Sponsored Research Grant from Anixa Biosciences Inc. (VKT), and from Philanthropic Funding (VKT).

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