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 (Peptide32-40 and Peptide175-183) 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.

中文翻译：

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具有来自犬乳腺肿瘤组织的 MHC I 类结合基序的 MMP-7 衍生肽在 BALB/c 小鼠中引发强烈的抗原特异性 T 细胞反应。

基质金属蛋白酶（MMP）诱导的细胞外基质蛋白和基底膜的蛋白水解改变是肿瘤进展和转移的关键。基质金属蛋白酶-7 (Matrilysin) 是 MMP 家族中最小的成员，其表现也非常相似；因此作为抗肿瘤免疫疗法的潜在候选者。相反，作为一种内源性肿瘤相关抗原 (TAA)，针对 MMP-7 进行免疫接种具有挑战性。但基于MMP-7的异种疫苗可以克服基于TAA的常规疫苗用于抗肿瘤免疫治疗时经常遇到的免疫原性和免疫耐受性差的障碍。这为研究 MMP-7 衍生的主要组织相容性复合物 (MHC) 结合肽的潜力铺平了道路，以引发精确的表位特异性 T 细胞反应，从而将其纳入抗肿瘤疫苗配方中。也许它也开辟了实现基于多个表位的广泛和通用细胞免疫的道路。在当前的实验中，采用免疫信息学方法来鉴定具有 MHC I 类结合基序的假定的犬基质蛋白酶 7 (cMMP-7) 衍生肽，这些肽可以在 BALB/c 小鼠中引发有效的抗原特异性免疫反应。使用 cMMP-7 DNA 疫苗进行免疫诱导了强烈的 CD8+ 细胞毒性 T 淋巴细胞 (CTL) 和 Th1 型反应，并在 BALB/c 小鼠中产生高水平的γ干扰素 (IFN-γ)。在用 cMMP-7 DNA 疫苗免疫的小鼠中，从 cMMP-7 中鉴定出的两种推定的 MHC-I 结合九聚肽（肽 32-40 和肽 175-183）可诱导显着的淋巴细胞增殖，同时 CD8+ T 细胞产生 IFN-γ。 。目前的观察结果描述了两种 cMMP-7 衍生的九肽的免疫原性潜力，可用于小鼠模型中异种疫苗介导的抗肿瘤免疫治疗。