MMP-7 derived peptides with MHC class-I binding motifs from canine mammary tumor tissue elicit strong antigen-specific T-cell responses in BALB/c mice

• Published in: Molecular and cellular biochemistry Vol. 476; no. 1; pp. 311 - 320
• Main Authors: Yadav, Pavan Kumar, Gupta, Shishir Kumar, Kumar, Saroj, Ghosh, Mayukh, Yadav, Brijesh Singh, Kumar, Dinesh, Kumar, Ajay, Saini, Mohini, Kataria, Meena
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.01.2021; Springer; Springer Nature B.V
• Subjects: Animals; Antigen (tumor-associated); Antigenic determinants; Antigens; Antigens, Neoplasm - metabolism; Binding; Biochemistry; Biomedical and Life Sciences; Breast cancer; Cancer Vaccines; Cardiology; CD8 antigen; Cell Line, Tumor; Cell Proliferation; Cell-mediated immunity; Computational Biology; Cytotoxicity; Deoxyribonucleic acid; DNA; DNA vaccines; Dogs; Epitopes; Epitopes - chemistry; Extracellular matrix; Female; HEK293 Cells; Histocompatibility Antigens Class I - immunology; Humans; Immune response; Immunization; Immunogenicity; Immunoglobulin G - immunology; Immunological tolerance; Immunology; Immunotherapy; Immunotherapy - methods; Interferon; Interferon-gamma; Life Sciences; Lymphocyte Activation; Lymphocytes; Lymphocytes T; Major histocompatibility complex; Mammary gland; Mammary Glands, Animal - metabolism; Matrilysin; Matrix metalloproteinase; Matrix Metalloproteinase 7 - metabolism; Matrix metalloproteinases; Medical Biochemistry; Metastases; Mice; Mice, Inbred BALB C; Oncology; Peptides; Peptides - chemistry; Protein Binding; Proteolysis; T cells; T-Lymphocytes - cytology; T-Lymphocytes - immunology; T-Lymphocytes, Cytotoxic - immunology; Tumors; Vaccines; γ-Interferon; Matrix metalloproteinase-7; Mammary tumor; Major histocompatibilty complex; Xenogeinic DNA vaccine; Immunoinformatics
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1007/s11010-020-03908-2

Matrix Metalloproteinases (MMPs)-induced altered proteolysis of extracellular matrix proteins and basement membrane holds the key for tumor progression and metastasis. Matrix metalloproteinases-7 (Matrilysin), the smallest member of the MMP family also performs quite alike; thus serves as a potential candidate for anti-tumor immunotherapy. Conversely, being an endogenous tumor-associated antigen (TAA), targeting MMP-7 for immunization is challenging. But MMP-7-based xenovaccine can surmount the obstacle of poor immunogenicity and immunological tolerance, often encountered in TAA-based conventional vaccine for anti-tumor immunotherapy. This paves the way for investigating the potential of MMP-7-derived major histocompatibility complex (MHC)-binding peptides to elicit precise epitope-specific T-cell responses towards their possible inclusion in anti-tumor vaccine formulations. Perhaps it also ushers the path of achieving multiple epitope-based broad and universal cellular immunity. In current experiment, an immunoinformatics approach has been employed to identify the putative canine matrix matelloproteinases-7 (cMMP-7)-derived peptides with MHC class-I-binding motifs which can elicit potent antigen-specific immune responses in BALB/c mice. Immunization with the cMMP-7 DNA vaccine induced a strong CD8 + cytotoxic T lymphocytes (CTLs) and Th1- type response, with high level of gamma interferon (IFN-γ) production in BALB/c mice. The two identified putative MHC-I-binding nonameric peptides (Peptide 32-40 and Peptide 175-183 ) from cMMP-7 induced significant lymphocyte proliferation along with the production of IFN-γ from CD8 + T-cells in mice immunized with cMMP-7 DNA vaccine. The current observation has depicted the immunogenic potential of the two cMMP-7-derived nonapeptides for their possible exploitation in xenovaccine-mediated anti-tumor immunotherapy in mouse model.