Cancer Regression in Patients After Transfer of Genetically Engineered Lymphocytes
Top Cited Papers
- 6 October 2006
- journal article
- clinical trial
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 314 (5796), 126-129
- https://doi.org/10.1126/science.1129003
Abstract
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.Keywords
This publication has 19 references indexed in Scilit:
- Enhanced Antitumor Activity of Murine-Human Hybrid T-Cell Receptor (TCR) in Human Lymphocytes Is Associated with Improved Pairing and TCR/CD3 StabilityCancer Research, 2006
- Recognition of Fresh Human Tumor by Human Peripheral Blood Lymphocytes Transduced with a Bicistronic Retroviral Vector Encoding a Murine Anti-p53 TCRThe Journal of Immunology, 2005
- Removal of homeostatic cytokine sinks by lymphodepletion enhances the efficacy of adoptively transferred tumor-specific CD8+ T cellsThe Journal of Experimental Medicine, 2005
- Transfer of a TCR Gene Derived from a Patient with a Marked Antitumor Response Conveys Highly Active T-Cell Effector FunctionsHuman Gene Therapy, 2005
- Adoptive Cell Transfer Therapy Following Non-Myeloablative but Lymphodepleting Chemotherapy for the Treatment of Patients With Refractory Metastatic MelanomaJournal of Clinical Oncology, 2005
- Long-term in vivo provision of antigen-specific T cell immunity by programming hematopoietic stem cellsProceedings of the National Academy of Sciences, 2005
- Cancer Regression and Autoimmunity in Patients After Clonal Repopulation with Antitumor LymphocytesScience, 2002
- T-cell-receptor gene therapyNature Reviews Immunology, 2002
- A New Era for Cancer Immunotherapy Based on the Genes that Encode Cancer AntigensImmunity, 1999
- T lymphocytes with a normal ADA gene accumulate after transplantation of transduced autologous umbilical cord blood CD34+ cells in ADA-deficient SCID neonatesNature Medicine, 1998