Phase I/II trial evaluating combined radiotherapy and in-situ gene therapy with or without hormonal therapy in the treatment of prostate cancer-an interim report on PSA response and biopsy data

Teh, Bin S.; Ayala, Gustavo; Mai, W.; Vlachaki, María T.; Caillouet, James; Davis, Marilyn; Wheeler, Mike; Miles, Brian J.; Kadmon, Dov; Aguilar-Cordova, L; Woo, Shiao Y.; Carpenter, L. Steven; Chiu, J. Kam; Lu, Haiquan; Thompson, Timothy C.; Aguilar-Córdova, Estuardo; Butler, E. Brian

doi:10.1016/s0360-3016(02)03295-9

Cited by 2 publications

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“…[9][10][11] Multiple clinical trials in men with this gene therapeutic approach have revealed necrosis within prostate cancer lesions in preference to adjacent normal prostatic tissues, 12 increased immune cells 12,13 and, when combined with radiation, an increase in the frequency of biopsies without evidence of cancer. 14 Additional studies have confirmed that intraprostatic adenoviral vector-mediated HSV-tk followed by systemic GCV treatment leads to increased numbers of HLA DR þ CD8 þ T cells in the peripheral blood of treated men. 13,15 We have also tested another active vaccine approach involving the immunomodulatory gene IL-12.…”

Section: Introductionmentioning

confidence: 90%

Therapeutic effects of adoptive splenocyte transfer following in situ AdIL-12 gene therapy in a mouse prostate cancer model

et al. 2005

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We developed a preclinical prostate cancer model to study the feasibility of adoptive immunotherapy for residual tumor following neo-adjuvant in situ adenoviral-vector-mediated interleukin 12 (AdIL-12) gene therapy. Splenocytes were obtained from mice with orthotopic 178-2 BMA metastatic mouse prostate cancers treated previously with AdIL-12, or a vector with the IL-12 genes plus the costimulatory gene B7-1 (AdIL-12/B7), or a control gene (Adbgal). The splenocytes were subsequently injected intravenously into syngeneic mice bearing orthotopic 178-2 BMA tumors generated 3 days previously. Significant orthotopic tumor growth suppression was achieved with splenocytes derived from mice whose tumors had been injected with AdIL-12 compared to splenocytes from control Adbgal mice (P ¼ 0.0005) and splenocytes from AdIL-12/B7-treated mice significantly suppressed spontaneous lung metastases compared to splenocytes from control mice (P ¼ 0.0356). Adoptive transfer of splenocytes from either AdIL-12 (P ¼ 0.004) or AdIL-12/B7 (P ¼ 0.009)-treated mice significantly prolonged survival relative to controls. Transfer of NK and tumor-specific CTL activities was detected and depletion of CD4 þ and CD8 þ T cells by in vitro antibody-mediated complement lysis of the splenocytes prior to injection abrogated the effects. Systemic IL-12 administration delivered by intramuscular AdIL-12 injection enhanced the antitumor effects of adoptive splenocyte transfer and boosted the CTL response. Our data provide evidence that this form of adoptive immunotherapy can enhance the effectiveness of neo-adjuvant in situ IL-12 gene therapy in cases of persistent malignancy.

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Section: Introductionmentioning

confidence: 90%

Therapeutic effects of adoptive splenocyte transfer following in situ AdIL-12 gene therapy in a mouse prostate cancer model

et al. 2005

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“…It has been suggested that injecting increasing amounts of vector into hypoechoic regions of the 19 prostate might be appropriate, as these regions are increasingly correlated with cancer…”

Section: Efficacy: Vector Distributionmentioning

confidence: 99%

Phase I Trial of Adenovirus-Mediated IL-12 Gene Transduction in Patients With Radiorecurrent Prostate Cancer

Hall¹

2004

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Public reporting burden for this collection of infonnation is estinMatd to average 1 hour per response, including the time for reviewing Instructions, searching existing data sources, gathering and meintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Washington Headquarters Services, Directorate for Information Operations and Reports, 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302, and to the Office of Management and Budget, Paperwork Reduction Project (0704-0188), Washington, DC 20503 AGENCY USE ONLY REPORT DATE REPORT TYPE AND DATES COVERED

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Phase I/II trial evaluating combined radiotherapy and in-situ gene therapy with or without hormonal therapy in the treatment of prostate cancer-an interim report on PSA response and biopsy data

Cited by 2 publications

References 0 publications

Therapeutic effects of adoptive splenocyte transfer following in situ AdIL-12 gene therapy in a mouse prostate cancer model

Therapeutic effects of adoptive splenocyte transfer following in situ AdIL-12 gene therapy in a mouse prostate cancer model

Phase I Trial of Adenovirus-Mediated IL-12 Gene Transduction in Patients With Radiorecurrent Prostate Cancer

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