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Báo cáo sinh học: " AAV2-mediated in vivo immune gene therapy of solid tumours"

Tuyển tập các báo cáo nghiên cứu về sinh học được đăng trên tạp chí sinh học Journal of Biology đề tài: AAV2-mediated in vivo immune gene therapy of solid tumours | Collins et al. Genetic Vaccines and Therapy 2010 8 8 http www.gvt-journal.eom content 8 1 8 GENETIC VACCINES AND THERAPY RESEARCH Open Access AAV2-mediated in vivo immune gene therapy of solid tumours 1.2 1 2 3 4 Sara A Collins 1 Alexandra Buhles Martina F Scallan Patrick T Harrison Deirdre M O Hanlon Gerald C O Sullivan1 Mark Tangney1 Abstract Background Many strategies have been adopted to unleash the potential of gene therapy for cancer involving a wide range of therapeutic genes delivered by various methods. Immune therapy has become one of the major strategies adopted for cancer gene therapy and seeks to stimulate the immune system to target tumour antigens. In this study the feasibility of AAV2 mediated immunotherapy of growing tumours was examined in isolation and combined with anti-angiogenic therapy. Methods Immune-competent Balb C or C57 mice bearing subcutaneous JBS fibrosarcoma or Lewis Lung Carcinoma LLC tumour xenografts respectively were treated by intra-tumoural administration of AAV2 vector encoding the immune up-regulating cytokine granulocyte macrophage-colony stimulating factor GM-CSF and the co-stimulatory molecule B7-1 to subcutaneous tumours either alone or in combination with intra-muscular IM delivery of AAV2 vector encoding Nk4 14 days prior to tumour induction. Tumour growth and survival was monitored for all animals. Cured animals were re-challenged with tumourigenic doses of the original tumour type. In vivo cytotoxicity assays were used to investigate establishment of cell-mediated responses in treated animals. Results AAV2-mediated GM-CSF B7-1 treatment resulted in a significant reduction in tumour growth and an increase in survival in both tumour models. Cured animals were resistant to re-challenge and induction of T cell mediated anti-tumour responses were demonstrated. Adoptive transfer of splenocytes to naive animals prevented tumour establishment. Systemic production of Nk4 induced by intra-muscular IM delivery of Nk4 .