Anti-tumour activity against B16-F10 melanoma with a GM-CSF secreting allogeneic tumour cell vaccine

Kayaga, J.; Souberbielle, Bernard; Sheikh, Nadeem A.; Morrow, W. J. W.; Scott-Taylor, Tim H.; Vile, Richard G.; Dalgleish, Angus

doi:10.1038/sj.gt.3300961

Cited by 54 publications

(46 citation statements)

References 33 publications

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“…These results can be compared with those of other authors who have obtained similar patterns of response employing viral vectors to transduce cells, and can be interpreted as the establishment of an immunologic memory affording long-term protection against tumor recurrence or metastasis. 1,4,17 GM-CSF has been found to be helpful in not only genetically modified tumor cells (clones) but also in fresh cytokine-secreting cells. It is important to point out that it is difficult to keep patient cells in vitro for long periods of time.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, it has been demonstrated that the amount of GM-CSF secreted by cell vaccines is critical to the magnitude of the immune response generated. 17,18 Thus, it might be inferred that if lower levels fail to induce strong antitumor immunity, excessively high levels might produce adverse effects. 24,44 In addition, we should also consider that the transfected cell types after tissue treatment as well as the time course of cytokine production with respect to antigen presentation could play a role in mediating tolerance rather than immune response stimulation.…”

Section: Discussionmentioning

confidence: 99%

“…16 In the present study, we have chosen GM-CSF and IL-4 for their purported different roles in immune system stimulation. [17][18][19] Accordingly, GM-CSF induces high antibody titers and T-cell proliferation, 20 even after allogeneic T-cell-depleted bone marrow transplantation. 21 Cytokine IL-4 in turn promotes the development of Th 2 cells and increases the production of antibodies and MHC class I and ICAM-1 expression in transfected cells, 22 although it could suppress CTL activity.…”

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confidence: 99%

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Complete tumor prevention by engineered tumor cell vaccines employing nonviral vectors

Moret

Díaz²,

Calle³

et al. 2003

Cancer Gene Ther

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We report that 100% mice survival after tumor challenge is achieved with cytokine-engineered cells employing nonviral lipoplexes and without using viral vectors. We describe this effect with cytokine-secreting tumor cell vaccines, based on cell clones or fresh transfected cells. Tumor cells were transfected with murine granulocyte-macrophage colony-stimulating factor (GM-CSF) or IL-4 plasmids employing the cationic lipid DOTAP, were irradiated (150 Gy) and kept frozen until use. The transfection efficacy was analyzed by qRT-PCR and flow cytometry. Vaccination induced potent antitumor rejection, resulting in 100% mice survival. Furthermore, the antitumor immunity was long lasting, since a two-fold survival delay was observed in mice after tumor rechallenge (6 months later). While cell clones secreting GM-CSF were the most effective in wild-type tumor cell rejection, little or no effect was observed with clones secreting IL-4. We found similar antitumor efficacy employing fresh transfected cells by nonviral procedures, demonstrating that cells genetically modified by nonviral vectors (both clones and fresh transfected cells) are a safe and efficient tool for antitumor vaccines. These vaccines allow us to achieve the highest antitumor efficacy based on nonviral gene therapy techniques. In addition, the vaccination success with fresh transfected cells simplifies the procedure and provides new insights into the clinical application of nonviral gene therapy procedures.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Complete tumor prevention by engineered tumor cell vaccines employing nonviral vectors

Moret

Díaz²,

Calle³

et al. 2003

Cancer Gene Ther

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“…It promotes tumor regression and has long been used as a potent cancer vaccine. [12][13][14] If an immunological component could contribute to a bystander-killing effect in the colon cancer system, combination gene therapy using GM-CSF transfection could synergistically improve the efficacy of the HSV-TK/GCV gene therapy system. However, in combination gene therapy, the route of delivery for each gene may have implications for efficacy, especially if a cell suicide gene such as HSV-TK is employed.…”

mentioning

confidence: 99%

Herpes simplex virus thymidine kinase and granulocyte macrophage colony-stimulating factor combination gene therapy in a murine CT26 cell colon cancer model

et al. 2004

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We evaluated the antitumor effects of combination gene therapy on CT26 mouse colon cancer cells, using the genes for herpes simplex virus thymidine kinase gene HSV-TK combined with granulocyte macrophage colony-stimulating factor (GM-CSF) compared with HSV-TK alone. Cells, unmodified or retrovirally transduced with HSV-TK or GM-CSF, were inoculated subcutaneously into syngeneic BALB/c mice in various combinations. HSV-TK and GM-CSF were also delivered using different routes (in separate cells vs doubly transfected single cells). Both HSV-TK (with i.p. ganciclovir -GCV -treatment) and GM-CSF genes had independent antitumor effects, and given together they caused significant reduction in tumor volumes compared with the HSV-TK gene alone (Po0.001). Following GCV treatment, however, the treated/control ratios for tumor volumes were not different between tumors containing either HSV-TK alone or both genes (0.27 vs 0.25, respectively). Thus, the presence of GM-CSF did not increase the bystander effect of HSV-TK. Tumors receiving genes transferred in separate cells tended to be more consistently suppressed after GCV treatment than when both genes were transferred in the same cells, although this was not statistically significant. Thus, combination GM-CSF and HSV-TK gene therapy produced greater therapeutic efficacy than HSV-TK alone, but the bystander effect was not enhanced by GM-CSF.

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“…Animal tumor models suggest, however, that allogeneic responses may actually enhance the development of tumor protection against syngeneic tumors in vivo. [2][3][4][5][6] Furthermore, it was shown that an allogeneic response supported the generation of tumor-antigen specific T cells that were capable of eliminating established metastases in a murine model. 6,7 In order to assess the feasibility of using an allogeneic strategy for vaccination of patients with metastatic RCC, that proliferated over extended periods of time in mixed lymphocyte tumor cell (MLTC) cultures.…”

Section: Introductionmentioning

confidence: 99%

Expression of B7.1 (CD80) in a renal cell carcinoma line allows expansion of tumor-associated cytotoxic T lymphocytes in the presence of an alloresponse

et al. 2000

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We have selected a well-characterized human renal cell carcinoma (RCC) line as the basis for development of a genetically engineered tumor cell vaccine to be applied in an allogeneic setting. This cell line was genetically modified by retroviral transduction to express B7.1 costimulatory molecules. The unmodified tumor cells and B7.1-expressing tumor cells were compared for their ability to induce tumorassociated responses in allogeneic peripheral blood mononuclear cells (PBMC) of two normal control donors having single MHC class I allele matches with the tumor cells. PBMC primed using B7.1-modified tumor cells showed a preponderance of CD3 + CD8 + cytotoxic T lymphocytes (CTL)

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Anti-tumour activity against B16-F10 melanoma with a GM-CSF secreting allogeneic tumour cell vaccine

Cited by 54 publications

References 33 publications

Complete tumor prevention by engineered tumor cell vaccines employing nonviral vectors

Complete tumor prevention by engineered tumor cell vaccines employing nonviral vectors

Herpes simplex virus thymidine kinase and granulocyte macrophage colony-stimulating factor combination gene therapy in a murine CT26 cell colon cancer model

Expression of B7.1 (CD80) in a renal cell carcinoma line allows expansion of tumor-associated cytotoxic T lymphocytes in the presence of an alloresponse

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