TY - JOUR
T1 - Vaccine-induced CD8 T cells are redirected with peptide-MHC class I-IgG antibody fusion proteins to eliminate tumor cells in vivo
AU - Fischer, Cornelia
AU - Munks, Michael W.
AU - Hill, Ann B.
AU - Kroczek, Richard A.
AU - Bissinger, Stefan
AU - Brand, Verena
AU - Schmittnaegel, Martina
AU - Imhof-Jung, Sabine
AU - Hoffmann, Eike
AU - Herting, Frank
AU - Klein, Christian
AU - Knoetgen, Hendrik
N1 - Publisher Copyright:
© 2020 The Author(s). Published with license by Taylor & Francis Group, LLC.
PY - 2020/1/1
Y1 - 2020/1/1
N2 - 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.
AB - 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.
KW - B16 lung metastases
KW - CMV
KW - Cancer immunotherapy
KW - MHCI restricted T-cell activation
KW - anti-viral CD 8 T cells
KW - antibody fusion
KW - major histocompatibility class I
KW - single peptide vaccination
KW - targeted T-cell recruiter
KW - tumor cell elimination
KW - viral mimicry on cancer cells
UR - http://www.scopus.com/inward/record.url?scp=85095577289&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85095577289&partnerID=8YFLogxK
U2 - 10.1080/19420862.2020.1834818
DO - 10.1080/19420862.2020.1834818
M3 - Article
C2 - 33151105
AN - SCOPUS:85095577289
SN - 1942-0862
VL - 12
JO - mAbs
JF - mAbs
IS - 1
M1 - 1834818
ER -