Immunogenicity and antitumor efficacy of a novel human PD-1 B-cell vaccine (PD1-Vaxx) and combination immunotherapy with dual trastuzumab/pertuzumab-like HER-2 B-cell epitope vaccines (B-Vaxx) in a syngeneic mouse model

Pravin T.P. Kaumaya, Linlin Guo, Jay Overholser, Manuel L. Penichet, Tanios Bekaii-Saab

Research output: Contribution to journalArticlepeer-review

Abstract

Therapeutic blockade of PD-1/PD-L1 signaling with monoclonal antibodies (mAbs) has shown clinical success and activity across a broad set of cancer subtypes. However, monotherapy with PD-1/PD-L1 inhibitors are only effective in a subset of patients and ongoing studies show efficacy of treatment depends on a combinatorial approach. Contrary to mAbs chimeric B-cell cancer vaccines incorporating a “promiscuous” T-cell epitope have the advantage of producing a polyclonal B-cell antibody that can potentially induce memory B- and T-cell responses, while reducing immune evasion and suppression. Here, we describe a novel PD-1 B-cell peptide epitope vaccine (amino acid 92–110; PD1-Vaxx) linked to a measles virus fusion peptide (MVF) amino acid 288–302 via a four amino acid residue (GPSL) emulsified in Montanide ISA 720VG that aims to induce the production of polyclonal antibodies that block PD-1 signaling and thus trigger anticancer effects similar to nivolumab. In preclinical studies, the PD1-Vaxx outperformed the standard anti-mouse PD-1 antibody (mAb 29 F.1A12) in a mouse model of human HER-2 expressing colon carcinoma. Furthermore, the combination of PD1-Vaxx with combo HER-2 peptide vaccine (B-Vaxx) showed enhanced inhibition of tumor growth in colon carcinoma BALB/c model challenged with CT26/HER-2 cells -. The PD-1 or combined vaccines were safe with no evidence of toxicity or autoimmunity.

Original languageEnglish (US)
Article number1818437
JournalOncoImmunology
Volume9
Issue number1
DOIs
StatePublished - Jan 1 2020

Keywords

  • B-cell epitopes
  • CT26 carcinoma
  • HER-2
  • Immuno-oncology
  • PD-1
  • PD-L1
  • nivolumab; CT26/HER-2 model
  • peptide cancer vaccines

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology

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