Cancer Regression in Patients After Transfer of Genetically Engineered Lymphocytes

作者：Richard A. Morgan, Mark E. Dudley, John R. Wunderlich, Marybeth S. Hughes, James Chih‐Hsin Yang, Richard Mark Sherry, Richard Eldon Royal, Suzanne Louise Topalian, Udai S. Kammula, Nicholas P. Restifo, Zhili Zheng, Azam V. Nahvi, Christiaan R. de Vries, Linda J. Rogers-Freezer, Sharon A. Mavroukakis, Steven A. Rosenberg · 发表于：Science · 年份：2006 · DOI：10.1126/science.1129003 · 被引用次数：2607 · 研究领域：CAR-T cell therapy research、Immunotherapy and Immune Responses、Virus-based gene therapy research

Through the adoptive transfer of lymphocytes after host immunodepletion, it is possible to mediate objective cancer regression in human patients with metastatic melanoma. However, the generation of tumor-specific T cells in this mode of immunotherapy is often limiting. Here we report the ability to specifically confer tumor recognition by autologous lymphocytes from peripheral blood by using a retrovirus that encodes a T cell receptor. Adoptive transfer of these transduced cells in 15 patients resulted in durable engraftment at levels exceeding 10% of peripheral blood lymphocytes for at least 2 months after the infusion. We observed high sustained levels of circulating, engineered cells at 1 year after infusion in two patients who both demonstrated objective regression of metastatic melanoma lesions. This study suggests the therapeutic potential of genetically engineered cells for the biologic therapy of cancer.