Vaccine-induced CD8 T cells are redirected with peptide-MHC class I-IgG antibody fusion proteins to eliminate tumor cells in vivo

Cornelia Fischer, Michael W. Munks, Ann B. Hill, Richard A. Kroczek, Stefan Bissinger, Verena Brand, Martina Schmittnaegel, Sabine Imhof-Jung, Eike Hoffmann, Frank Herting, Christian Klein, Hendrik Knoetgen

Research output: Contribution to journalArticlepeer-review

Abstract

Simulating a viral infection in tumor cells is an attractive concept to eliminate tumor cells. We previously reported the molecular design and the in vitro potency of recombinant monoclonal antibodies fused to a virus-derived peptide MHC class I complex that bypass the peptide processing and MHC loading pathway and directly displays a viral peptide in an MHC class I complex on the tumor cell surface. Here, we show that a vaccination-induced single peptide-specific CD8 T cell response was sufficient to eliminate B16 melanoma tumor cells in vivo in a fully immunocompetent, syngeneic mouse tumor model when mice were treated with mouse pMHCI-IgGs fusion proteins targeting the mouse fibroblast activation protein. Tumor growth of small, established B16 lung metastases could be controlled. The pMHCI-IgG had similar potency as an analogous pan-CD3 T-cell bispecific antibody. In contrast to growth control of small tumors, none of the compounds controlled larger solid tumors of MC38 cancer cells, despite penetration of pMHCI-IgGs into the tumor tissue and clear attraction and activation of antigen-specific CD8 T cells inside the tumor. pMHCI-IgG can have a similar potency as classical pan-T-cell recruiting molecules. The results also highlight the need to better understand immune suppression in advanced solid tumors.

Original languageEnglish (US)
Article number1834818
JournalmAbs
Volume12
Issue number1
DOIs
StatePublished - Jan 1 2020

Keywords

  • B16 lung metastases
  • CMV
  • Cancer immunotherapy
  • MHCI restricted T-cell activation
  • anti-viral CD 8 T cells
  • antibody fusion
  • major histocompatibility class I
  • single peptide vaccination
  • targeted T-cell recruiter
  • tumor cell elimination
  • viral mimicry on cancer cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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