Induction of T-cell antitumor immunity and protection against tumor growth by secretion of soluble human CD70 molecules

• Published in: Cancer gene therapy Vol. 11; no. 7; pp. 497 - 507
• Main Authors: Cormary, Carine, Gonzalez, Ricardo, Faye, Jean-Charles, Favre, Gilles, Tilkin-Mariamé, Anne-Françoise
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.07.2004
• Subjects: Animals; Antigens, CD - genetics; Antigens, CD - immunology; Antigens, CD - metabolism; Antitumor activity; Care and treatment; CD27 Ligand; CD70 antigen; Cell Line; Cell Line, Tumor; Cell Membrane - metabolism; Cell Proliferation; Cellular signal transduction; Coculture Techniques; Costimulator; Culture Media, Conditioned - chemistry; Female; Fibroblasts; Fibroblasts - metabolism; Fibroblasts - radiation effects; Fibroblasts - secretion; Fibroblasts - transplantation; Gene therapy; Genetic aspects; Health aspects; Immunity; Immunocompetence; Injections; Lymphocyte Activation; Lymphocytes T; Mammary Neoplasms, Animal - immunology; Mammary Neoplasms, Animal - metabolism; Mammary Neoplasms, Animal - pathology; Mammary Neoplasms, Animal - therapy; Membrane Proteins - genetics; Membrane Proteins - immunology; Membrane Proteins - metabolism; Membrane Proteins - secretion; Methods; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Transplantation; Spleen - cytology; Spleen - immunology; Splenocytes; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Transfection; Transplantation, Homologous; Tumor cells; Tumors; France
• ISSN: 0929-1903; 1476-5500
• DOI: 10.1038/sj.cgt.7700708

One of the strategies to promote an antitumor response is the genetic modification of tumor cells to induce expression of costimulatory molecules. We have tested the capacity of a soluble form of CD70 molecule (sCD70). After construction of a vector carrying the sCD70, we obtained stable sCD70-secreting TS/A tumor cells and allogenic MC57 fibroblasts. In all, 45% of wild-type (wt) tumors were rejected in immunocompetent mice when transfected sCD70-secreting cells were injected three times in the periphery of the wt tumors. Furthermore, the sCD70-secreting TS/A cells induced a protective memory against wt TS/A tumor growth: 70% of the wt tumors used for the challenge were rejected by mice, which had rejected tumors 45 days before in the presence of sCD70-secreting TS/A cells. It was also shown that in vitro mock TS/A tumor cell proliferation was inhibited by splenocytes harvested from mice injected with TS/A cells expressing CD70. Growth kinetics of wt TS/A tumors in immunocompetent versus nude mice suggested that T lymphocytes were implicated in the antitumor response, which was confirmed by membrane expression of specific markers. The data suggest that injection of genetically transfected cells secreting sCD70 in the periphery of wt TS/A tumors induces T-cell-mediated inhibition of tumor growth and builds up a protective antitumor memory.