【摘 要】
:
We have completed four small Phase Ⅰ and Ⅱ clinical trials (a total of 64 patients; 126 doses) using Cytotoxic T Lymphocytes (CTLs) generated against malignant melanoma-specific peptides.We achieved a
【机 构】
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Drug Discovery Cell Therapy Johnson & Johnson Pharmaceutical R & D, Cell Therapy Team, La Jolla CA
【出 处】
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BIT‘s2nd Annual World Cancer Congess-2009 (2009第二届癌症大会)
论文部分内容阅读
We have completed four small Phase Ⅰ and Ⅱ clinical trials (a total of 64 patients; 126 doses) using Cytotoxic T Lymphocytes (CTLs) generated against malignant melanoma-specific peptides.We achieved an overall objective response rate of 18.5%, and 2-year survival rate of 22%.The initial manufacturing protocol used in all four studies had several disadvantages; a manufacturing time of 5 weeks, an extremely labor intensive procedure, an open system of manufacturing, and a product expressing a phenotype which may have been sub-optimal.In an effort to prepare for large-scale Phase Ⅱ/Ⅲ clinical trials, we have incorporated several improvements to the overall manufacturing process.These include: 1) modifying the method of CD8+ T cell isolation, 2) enhancing the primary stimulation with peptide-loaded psoralen/UV treated Drosophila cells expressing human molecules, 3) restimulating effector cells with peptide-loaded antigen presenting cells and autologous feeder cells, 4) including an additional cytokine during ex vivo manufacturing, and 5) enclosing and automating the manufacturing process.These improvements shorten the manufacturing time from 5 weeks to 3 weeks, time critical to these Stage Ⅳ Melanoma patients with a predicted life expectancy of 6-9 months.The availability of this streamlined ex vivo process should allow for commercialization, thereby realizing the promise of cell-based immunotherapy as a treatment for cancer.
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