成果報告書詳細
管理番号20120000000938
タイトル*平成23年度中間年報 「基礎研究から臨床研究への橋渡し促進技術開発 橋渡し促進技術開発/癌特異的抗原受容体改変T細胞の輸注とがんワクチンによる複合的がん免疫療法の研究開発」
公開日2014/8/28
報告書年度2011 - 2011
委託先名タカラバイオ株式会社 国立大学法人三重大学 学校法人慶應義塾
プロジェクト番号P07022
部署名バイオテクノロジー・医療技術部
和文要約
英文要約Title: Development of comprehensive cancer immunotherapy utilizing adoptive transfer of tumor-specific TCR-engineered T cells and cancer vaccine (FY2010-2012) FY2011 Annual Report: 1-1. We confirmed the stability of 3 lots of GMP-grade retrovirus vector A for at most 36 months on -80 °C. In the clinical trial, five new patients were enrolled. Two patients completed the trial in cohort 1. Including one patient enrolled in 2010, neither adverse effects relating to the TCR-engineered T cell treatment nor risks relating to retrovirus, such as a reproductive retrovirus or clonality in transferred cells, were observed in all 3 patients in cohort 1. The trial progressed into cohort 2 after the approval by the committee for efficacy, safety, and dose escalation in Mie University. In the cohort 2, one patient dropped without adoptive cell transfer because of the progression of the disease, one patient received the cell transfer, and two patients stand by the cell transfer. Transferred T cells were detected in all patient’s peripheral blood by quantitative PCR analysis on inserted vector. From a tumor biopsy specimen of one patient in cohort 1, tumor infiltration of transferred cells were detected by quantitative PCR. The integration of Osaka University Hospital and Kitano Hospital in this trial to formulate a multiple-site clinical trial is in process. : 1-2. We manufactured the third lot of GMP-grade retrovirus vector B. We confirmed the stability of the GMP-grade retrovirus vector B for 12 months in -80 °C and 6 months in -40 °C. Three rounds of test-run for TCR-engineered T cells with retrovirus vector B was performed with satisfactory quality. We developed a mouse model of adoptive cell transfer with T cells engineered with siTCR vector, and in process to confirm the safety. We found that T cells stimulated with RetroNectin acquired multifunctionality and the capacity to resist apoptosis resulting in enhanced anti-tumor effect when adoptively transferred into tumor-bearing mice. We are in process to submit the application of a clinical protocol for TCR-gene therapy with vector B to Ministry of Health, Labour, and Welfare. Aiming the practical development of TCR-gene therapy with vector B, we continuously are discussing with PMDA. : 2. As described in section 1, transferred T cells were well detected in peripheral blood and in tumor tissue of enrolled patients. Utilizing the samples from immunotherapy clinical trials in multiple institutes, IL-6 and IL-8 (CXCL8) in serum were found as biomarkers that predict the unfavorable prognosis in patients who had undergone immunotherapy. We developed several new methods of immuno-monitering, such as multicolor tetramer, beads array mRNA, protein-beads array, and Cancer-Testis Antigen (CTA)-specific protein active array that contains 223 kinds of cancer-related proteins. We established an efficient method to generate specific T cells by mannose-coated liposome. We standardized ELISPOT assay for multiple-site trials.
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