Immunotherapy-induced antibodies to endogenous retroviral envelope glycoprotein confer tumor protection in mice.

Byong H Kang,Kelly D Moynihan,K Dane Wittrup,Darrell J Irvine,Noor Momin,Yingzhong Li,Murillo Silva

doi:10.1371/journal.pone.0248903

Abstract

Following curative immunotherapy of B16F10 tumors, ~60% of mice develop a strong antibody response against cell-surface tumor antigens. Their antisera confer prophylactic protection against intravenous challenge with B16F10 cells, and also cross-react with syngeneic and allogeneic tumor cell lines MC38, EL.4, 4T1, and CT26. We identified the envelope glycoprotein (env) of a murine endogenous retrovirus (ERV) as the antigen accounting for the majority of this humoral response. A systemically administered anti-env monoclonal antibody cloned from such a response protects against tumor challenge, and prophylactic vaccination against the env protein protects a majority of naive mice from tumor establishment following subcutaneous inoculation with B16F10 cells. These results suggest the potential for effective prophylactic vaccination against analogous HERV-K env expressed in numerous human cancers.

Highlights

Success of checkpoint blockade therapies in the past decade has clearly demonstrated the dominant role T cells play in an antitumor response and immunosurveillance [1, 2]
We report that two of the recognized antigens are products of endogenous ecotropic murine leukemia virus, with the envelope glycoprotein of eMLV as the dominant cell-surface antigen targeted by the immunotherapy-induced antibodies (iiAbs) in cured mice
We have previously observed that the combination immunotherapy termed AIPV causes robust tumor rejection and immunological memory in several mouse models resulting in successful rejection of a secondary subcutaneous rechallenge

Summary

Introduction

Success of checkpoint blockade therapies in the past decade has clearly demonstrated the dominant role T cells play in an antitumor response and immunosurveillance [1, 2]. The functional role of B cells and antibodies (Abs) in cancer remains less clear [3, 4]. High expression levels of B cell signature genes correlated with improved survival in patients with melanoma, lung adenocarcinoma, pancreatic adenocarcinoma, and head and neck squamous cell carcinoma, but with poor prognosis in patients with glioblastoma and clear cell renal cell carcinoma [5,6,7]. B cells have been shown to exert pro-tumor effects by promoting metastasis [8], angiogenesis [9], and contributing to an immunosuppressive tumor microenvironment [10,11,12].

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Conclusion