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

Cancer Gene Therapy volume 13, pages 91–98 (2006)Cite this article

Abstract

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 (Adβgal). 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 Adβgal mice (P=0.0005) and splenocytes from AdIL-12/B7-treated mice significantly suppressed spontaneous lung metastases compared to splenocytes from control mice (P=0.0356). Adoptive transfer of splenocytes from either AdIL-12 (P=0.004) or AdIL-12/B7 (P=0.009)-treated mice significantly prolonged survival relative to controls. Transfer of NK and tumor-specific CTL activities was detected and depletion of CD4+ and CD8+ 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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Acknowledgements

This work was supported by grants from the NCI (ROI-50588) and Specialized Program for Research Excellence (SPORE, P50-58204) and a grant from the DOD. Portions of this work were conducted in facilities provided by the Houston VA Medical Center.

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Authors and Affiliations

  1. Scott Department of Urology, Baylor College of Medicine, Houston, TX, USA

    T Saika, N Kusaka, V Mouraviev, T Satoh, T L Timme & T C Thompson

  2. Department of Urology, Okayama University Medical School, Okayama, Japan

    H Kumon

  3. Michael E. DeBakey VA Medical Center, Houston, TX, USA

    T L Timme & T C Thompson

  4. Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA

    T C Thompson

  5. Department of Radiology, Baylor College of Medicine, Houston, TX, USA

    T C Thompson

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  1. T Saika
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Correspondence to T C Thompson.

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Saika, T., Kusaka, N., Mouraviev, V. et al. Therapeutic effects of adoptive splenocyte transfer following in situ AdIL-12 gene therapy in a mouse prostate cancer model. Cancer Gene Ther 13, 91–98 (2006). https://doi.org/10.1038/sj.cgt.7700872

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