Vaccine-induced CD8 T cells are redirected with peptide-MHC class I-IgG antibody fusion proteins to eliminate tumor cells in vivo
| Autor: | Eike Hoffmann, Cornelia Fischer, Ann B. Hill, Martina Schmittnaegel, Stefan Bissinger, Michael W. Munks, Hendrik Knoetgen, Christian Klein, Richard A. Kroczek, Frank Herting, Sabine Imhof-Jung, Verena Brand |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
medicine.drug_class
medicine.medical_treatment Recombinant Fusion Proteins Immunology anti-viral CD 8 T cells Melanoma Experimental Cancer immunotherapy CD8-Positive T-Lymphocytes Major histocompatibility complex Monoclonal antibody Cancer Vaccines targeted T-cell recruiter 03 medical and health sciences antibody fusion tumor cell elimination Mice 0302 clinical medicine Immune system major histocompatibility class I Report MHC class I medicine Immunology and Allergy Cytotoxic T cell Animals 030304 developmental biology 0303 health sciences biology Chemistry Histocompatibility Antigens Class I CMV MHCI restricted T-cell activation Fusion protein B16 lung metastases Mice Inbred C57BL single peptide vaccination 030220 oncology & carcinogenesis Immunoglobulin G Cancer cell biology.protein Cancer research viral mimicry on cancer cells |
| Zdroj: | mAbs article-version (VoR) Version of Record |
| ISSN: | 1942-0870 1942-0862 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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