A Phase I Study of Vaccination with Autologous, Irradiated Melanoma Cells Engineered to Secrete Human Granulocyte-Macrophage Colony Stimulating Factor. Dana-Farber Cancer Institute, Boston, Massachusetts

Dranoff, Glenn; Soiffer, Robert J.; Lynch, Thomas J.; Mihm, M. C.; Jung, Keehoon; Kolesar, K; Liebster, L; Lam, Paula Yeng Po; Duda, Rosemary B.; Mentzer, S; Singer, Samuel; Tanabe, Kenneth K.; Johnson, Rebecca L.; Sober, Arthur J.; Bhan, Atul K.; Clift, Shirley M.; Cohen, Lawrence K.; Parry, Gordon; Rokovich, Joseph; Richards, Lisa A.; Drayer, Jan I.M.; Berns, Anton; Mulligan, Richard C.

doi:10.1089/hum.1997.8.1-111

Cited by 70 publications

(28 citation statements)

References 41 publications

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“…33 A pilot study of GM -CSF in MM given intratumorally produced local necrosis with an intense lymphocytic infiltration in biopsy samples in a small proportion of patients correlating with transient tumor regression. 9 We found marked areas of necrosis within tumors taken from mice treated with surgical debulking and the GM -CSF transfectant, compared to control tumors, implying that an active antitumoral process did occur.…”

Section: Discussionmentioning

confidence: 99%

The immune anti-tumor effects of GM-CSF and B7-1 gene transfection are enhanced by surgical debulking of tumor

et al. 2001

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Malignant mesothelioma ( MM ) is a solid tumor largely unresponsive to conventional therapies. Immunological gene therapy shows promise in murine models and human clinical trials; however, the role of surgery in combination with gene therapy has not been widely studied. The aim of this study was to determine if debulking surgery improved the effectiveness of gene therapy in a murine MM model. Mice were subcutaneously inoculated with the MM cell line, AC29, at two different sites, 4 days apart, to allow a surgical and distal site tumor to develop. Once tumors were established, the surgical site tumor was debulked and vaccination of syngeneic tumor transfectants encoding genes for IL -4, IL -2, GM -CSF, B7 -1 or allogeneic MHC molecules commenced at a site away from both tumors, and tumor growth was measured. Neither debulking surgery nor gene therapy alone delayed tumor growth. However, there was a clear delay of tumor growth when debulking surgery was combined with vaccination of tumor transfectants expressing B7 -1 or high levels of GM -CSF. Combinations of these two transfectants did not lead to a synergistic effect. This study demonstrates that debulking surgery can augment the immunostimulatory effects of immunological gene therapy and can delay tumor growth. This has implications for the future design of human gene therapy trials for solid tumors such as MM.

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Section: Discussionmentioning

confidence: 99%

The immune anti-tumor effects of GM-CSF and B7-1 gene transfection are enhanced by surgical debulking of tumor

et al. 2001

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“…Adoptive immunotherapy using autologous APCs may provide a strategy for enhanced immune responses reproducing that seen in early tumour growth. Alternatively, recruitment of endogenous naive DCs using GM-CSF to promote capture of vaccinated tumour peptides (Dranoff et al, 1997) could provide an effective anti-tumour strategy. It may also be possible to use the density of infiltrating CD1a + cells as a prognostic indicator by relating their density to survival and recurrence rates in longitudinal follow-up studies 5 and 10 years following surgical resection.…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical localization of CD1a-positive putative dendritic cells in human breast tumours

1999

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SummaryThe presence of a high number of infiltrating CD1a + cells in malignant neoplasms has been reported to be associated with an improved prognosis, reduced tumour recurrence and fewer metastases. This study identified a population of CD1a + cells within the lymphoid cell infiltrate in human ductal breast carcinoma (n = 52), which was significantly different from normal breast tissue, in which only two out of nine cases expressed CD1a + cells (P = 0.0192). In the majority of cases, the infiltrate was low compared with the number of macrophages and T cells present (results not shown). There was no correlation between the number of CD1a + cells and tumour grade, with all tumour grades expressing similar numbers of infiltrating CD1a + cells. There was clear evidence, however, that the CD1a + cells were closely associated with tumour cells. It is likely that CD1a + cells have a role in antigen capture and presentation in human tumours, and this study documents the density of CD1a + cells in a large sample of all histological grades of human breast carcinomas.

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“…Introduction of immunomodulatory genes into tumor cells to enhance immunogenicity and generate a tumor-specific immune response has been applied in the development of vaccines for solid tumors. 18,19 In particular, the expression of genes such as B7.1 (CD80) has been identified as a powerful means to increase the immunogenicity of malignant cells. 20,21 Rapid and efficient gene transfer into primary AML cells utilizing the VPC method thus becomes a potentially useful tool in the development of novel treatment strategies for AML.…”

Section: Introductionmentioning

confidence: 99%

Genetic manipulation of primitive leukemic and normal hematopoietic cells using a novel method of adenovirus-mediated gene transfer

et al. 1999

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A Phase I Study of Vaccination with Autologous, Irradiated Melanoma Cells Engineered to Secrete Human Granulocyte-Macrophage Colony Stimulating Factor. Dana-Farber Cancer Institute, Boston, Massachusetts

Cited by 70 publications

References 41 publications

The immune anti-tumor effects of GM-CSF and B7-1 gene transfection are enhanced by surgical debulking of tumor

The immune anti-tumor effects of GM-CSF and B7-1 gene transfection are enhanced by surgical debulking of tumor

Immunohistochemical localization of CD1a-positive putative dendritic cells in human breast tumours

Genetic manipulation of primitive leukemic and normal hematopoietic cells using a novel method of adenovirus-mediated gene transfer

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