Anti-Tumor Immunity Elicited by a Recombinant Vaccinia Virus Expressing CD70 (CD27L)

Lorenz, Matthias G.O.; Kantor, Judith A.; Schlom, Jeffrey; Hodge, James W.

doi:10.1089/10430349950018094

Cited by 65 publications

(36 citation statements)

References 28 publications

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“…Different protocols in human or murine models have already confirmed this using membrane expressed forms of CD70 molecules. 8,28,29 The results obtained in vitro concerning the inhibition of in vitro tumor proliferation were similar with the two forms of CD70-expressing cells. However, in our models, in vivo experiments showed that tumor rejection by immunocompetent mice is more efficient with CD70-secreting cells than with cells expressing membrane CD70.…”

Section: Discussionsupporting

confidence: 65%

“…Experiments carried out in many mice models, with costimulatory molecules, such as CD28, CD40 or CD27 and their respective ligands CD80, CD154 and CD70, have resulted in tumor rejection and generation of antitumor immunity against parental tumor cells. [6][7][8] CD70 is a type II transmembrane glycoprotein, a member of the tumor necrosis factor (TNF) superfamily, which includes CD154 and CD95. 9 Both human and murine T lymphocytes express CD70 and the CD27 ligand.…”

mentioning

confidence: 99%

“…13 This costimulation provokes production of various cytokines such as interleukin2 (IL-2) and interferon-g (IFN-g). 8 Recently, it was shown that CD27/CD70 interactions also play a role as a costimulatory factor in Tcell cytotoxicity involving the perforin/granzyme B pathway. 14 In several murine tumor models, it was shown that genetically transfected tumor cells expressing CD70 were able to enhance a specific T-cell response and in particular that of CD8 þ T lymphocytes mediating cytotoxic antitumor immunity.…”

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confidence: 99%

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

et al. 2004

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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.

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Section: Discussionsupporting

confidence: 65%

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confidence: 99%

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confidence: 99%

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

et al. 2004

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“…20 ± 22 The transfection of CD70 in some immunogenic murine tumor cells have been shown to induce tumor regression and to enhance an antitumor immunity T-cell mediated. 17,23,24 Furthermore, cotransfection of both CD70 and CD80 into the poorly immunogenic MCA 207 tumor cells in the presence of interleukin -12 ( IL-12) has been shown to enhance a protective antitumor immunity against parental tumor growth in a vaccination model. 17 Looking toward the treatment of human cancer, the present study aimed to establish a potent immunotherapy for tumors that lack apparent immunogenicity, and more specifically for such MHC -deficient expression tumor cells.…”

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confidence: 99%

The expression of CD70 and CD80 by gene-modified tumor cells induces an antitumor response depending on the MHC status

et al. 2000

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The expression of costimulatory molecules such as CD70 or CD80 by gene -modified tumor cells has been shown to enhance the antitumor immune response based mainly on T lymphocytes. However, most human tumors show defects of major histocompatibility complex ( MHC ) expression, preventing them from being recognized by MHC -restricted T cells. To investigate if coexpression of CD70 and CD80 costimulatory molecules induces comparable antitumor responses in low and high MHCexpressing tumor cells, we used two low immunogenic murine tumor models, the B16.F10 melanoma and the TS / A mammary adenocarcinoma cell lines expressing, respectively, low and high levels of MHC class I molecules. Transfection of both CD70 and CD80 genes resulted in an increased capacity of gene -modified tumor cells to costimulate in vitro the proliferation and cytokine production of optimally activated lymphoid cells. Coexpression of CD70 and CD80 by the two tumor cell lines, TS / A and B16.F10, resulted in both cases in partial regression of subcutaneous tumors. Immunochemical analysis and studies in nude mice showed that, even in the B16.F10 model, T cells had a significant role in the antitumor response induced by combining CD70 and CD80. However, rejection of the CD70 / CD80 -transfected tumor cells appeared more effective in the MHC class I high TS / A model, leading to a protection against parental tumor cells. B16.F10 and TS / A transfectants were then tested with fibroblasts genetically modified to secrete interleukin -12 ( IL -12 ) as a therapeutic vaccine in mice bearing parental tumors. In the two models tested, the injections of irradiated IL -12 and CD70 / CD80 gene -modified cells generated an antitumor response to established tumors leading to the slowing down of the tumor growth rate. Although the mechanisms remain to be defined, these findings suggest that the combination of several immuno -modulatory molecules could provide additional strategies for cancer immuno -gene therapy, even for MHC expression ± deficient tumors. Cancer Gene Therapy ( 2000 ) 7, 1543 ± 1556

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“…[37][38][39] When employed in vaccination strategies, transgenic expression of CD70 does induce antitumor immunity in solid tumor models. 40,41 In contrast in mice with residual lymphoblastic disease, transgenic expression of CD70 alone is not sufficient to induce an antineoplastic immune response, while the combination of CD70 and IL-2 expressed in vaccine cells affords significant but not complete protection. 42 Therefore, coexpression of CD70 with IL-2 in our current study seemed a highly suitable vaccine combination for the purpose of exploring potentially additive effects mediated by the HSV-1 amplicon vector itself.…”

Section: Hsv-1 Amplicons For Generation Of All Vaccinesmentioning

confidence: 99%

Herpes simplex virus type-1 amplicon vectors for vaccine generation in acute lymphoblastic leukemia

et al. 2005

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For leukemia vaccine generation, high-efficiency gene transfer is required to express immunomodulatory molecules that stimulate potent antileukemic immune responses. In this context, herpes simplex virus type-1 (HSV-1)-derived vectors have proven to be a promising tool for genetic modification of lymphoblastic leukemia cells. Yet, vector-associated viral protein expression might inadvertently modulate vaccine efficacy facilitating both immune evasion and immune stimulation. To explore the issue of immune-stimulation versus immune-suppression in immature lymphoblastic leukemia cells, two types of HSV-1 amplicon vectors, helper virus-dependent and helper virus-free that express the immunomodulatory molecules CD70 and IL-2, were compared with regard to their vector-associated immunomodulatory potential. We first established that lymphoblastic cell lines and primary acute lymphoblastic leukemia (ALL) cells express HSV receptor genes. Lymphoblastic cell lines were transduced with high efficiency, and in primary ALL cells high gene transfer rates of 47715 and 42714% were obtained with helper virus-dependent and -free HSV-1 amplicon vectors, respectively. The efficacy of the two amplicon vectors to induce antineoplastic responses was assessed in a vaccine setting in mice with pre-existing highly malignant lymphoblastic disease. Treatment of mice with vaccine cells transgenically expressing CD70+IL2 significantly suppressed lymphoblastic cell proliferation and improved survival. Of note, when helper virus-dependent HSV-1 amplicon vectors were used for vaccine preparation, the high immunogenic potential of the vector itself, in the absence of transgenic CD70+IL2 expression, seemed to be sufficient to mediate protection comparable to the antineoplastic response achieved by expression of immunomodulatory molecules. Thus for vaccine generation in B lymphoblastic leukemia, the immunogenic potential of HSV-1 helper virus-dependent amplicon vectors does provide additional benefit to the high transduction efficiency of HSV-1-derived vectors.

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Anti-Tumor Immunity Elicited by a Recombinant Vaccinia Virus Expressing CD70 (CD27L)

Cited by 65 publications

References 28 publications

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

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

The expression of CD70 and CD80 by gene-modified tumor cells induces an antitumor response depending on the MHC status

Herpes simplex virus type-1 amplicon vectors for vaccine generation in acute lymphoblastic leukemia

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