Lewis Jennifer D, Sullivan Laura A, Byrne Jennifer A, de Riese Werner, Bright Robert K
Department of Microbiology and Immunology, Texas Tech University Health Sciences Center, 3601 4th Street, Lubbock, TX 79430, USA.
Cancer Immunol Immunother. 2009 Aug;58(8):1337-49. doi: 10.1007/s00262-009-0659-x. Epub 2009 Jan 24.
Tumor protein D52 (TPD52) is involved in cellular transformation, proliferation and metastasis. TPD52 over expression has been demonstrated in several cancers including prostate, breast, and ovarian carcinomas. Murine TPD52 (mD52) has been shown to induce anchorage independent growth in vitro and metastasis in vivo, and mirrors the function and normal tissue expression patterns of the human orthologue of TPD52. We believe TPD52 represents a self, non-mutated tumor associated antigen (TAA) important for maintaining a transformed and metastatic cellular phenotype. The transgenic adeno-carcinoma of the mouse prostate (TRAMP) model was employed to study mD52 as a vaccine antigen. Naïve mice were immunized with either recombinant mD52 protein or plasmid DNA encoding the full-length cDNA of mD52. Following immunization, mice were challenged with a subcutaneous, tumorigenic dose of mD52 positive, autochthonous TRAMP-C1 tumor cells. Sixty percent of mice were tumor free 85 days post challenge with TRAMP-C1 when immunized with mD52 as a DNA-based vaccine admixed with soluble granulocyte-macrophage colony stimulating factor (GM-CSF). Survivors of the initial tumor challenge rejected a second tumor challenge given in the opposite flank approximately 150 days after the first challenge, and remained tumor free for more than an additional 100 days. The T cell cytokine secretion patterns from tumor challenge survivors indicated that a T(H)1-type cellular immune response was involved in tumor protection. These data suggest that mD52 vaccination induced a memory, cellular immune response that resulted in protection from murine prostate tumors that naturally over express mD52 protein.
肿瘤蛋白D52（TPD52）参与细胞转化、增殖和转移。TPD52的过表达已在包括前列腺癌、乳腺癌和卵巢癌在内的多种癌症中得到证实。小鼠TPD52（mD52）已被证明可在体外诱导不依赖贴壁生长并在体内诱导转移，并且反映了TPD52人类同源物的功能和正常组织表达模式。我们认为TPD52代表一种自身的、未发生突变的肿瘤相关抗原（TAA），对维持转化和转移的细胞表型很重要。采用小鼠前列腺转基因腺癌（TRAMP）模型来研究mD52作为疫苗抗原。用重组mD52蛋白或编码mD52全长cDNA的质粒DNA对未接触过抗原的小鼠进行免疫。免疫后，用皮下注射致瘤剂量的mD52阳性、原位TRAMP-C1肿瘤细胞对小鼠进行攻击。当用作为DNA疫苗并与可溶性粒细胞巨噬细胞集落刺激因子（GM-CSF）混合的mD52免疫时，60%的小鼠在接受TRAMP-C1攻击后85天无肿瘤。初次肿瘤攻击的幸存者在第一次攻击后约150天拒绝了在对侧腹进行的第二次肿瘤攻击，并在另外100多天内保持无肿瘤状态。肿瘤攻击幸存者的T细胞细胞因子分泌模式表明，T（H）1型细胞免疫反应参与了肿瘤保护。这些数据表明，mD52疫苗接种诱导了记忆性细胞免疫反应，从而对天然过表达mD52蛋白的小鼠前列腺肿瘤产生保护作用。
