CRISPR-engineered T cells in patients with refractory cancer

Edward A. Stadtmauer1,2, Joseph A. Fraietta1,3,4,5,6, Megan M. Davis3,5, Adam D. Cohen1,2, Kristy Weber1,7, Eric Lancaster8, Patricia Mangan2, Irina Kulikovskaya3, Minnal Gupta3, Fang Chen3, Lifeng Tian3, Vanessa Gonzalez3, Jun Xu3, In-Young Jung3,4, J. Joseph Melenhorst3,5,6, Gabriela Plesa3, Joanne Shea3, Tina Matlawski3, Amanda Cervini3, Avery L. Gaymon3, Stephanie Desjardins3, Anne Lamontagne3, January Salas-McKee3, Andrew D. Fesnak3,5, Donald L. Siegel3,5, Bruce L. Levine3,5, Julie K. Jadlowsky3, Regina M. Young3, Anne Chew3, Wei‐Ting Hwang9, Elizabeth O. Hexner1,2, Beatriz M. Carreno3,5,6, Christopher L. Nobles4, Frederic D. Bushman4, Kevin R. Parker10, Yanyan Qi11, Ansuman T. Satpathy10,11, Howard Y. Chang10,12, Yangbing Zhao3,5, Simon F. Lacey3,5, Carl H. June1,3,5,6
1Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
2Division of Hematology-Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
3Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
4Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
5Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
6Parker Institute for Cancer Immunotherapy, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
7Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
8Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
9Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
10Center for Personal Dynamic Regulomes, Stanford University School of Medicine, Stanford, CA, USA
11Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA
12Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA, USA

Tóm tắt

CRISPR takes first steps in humans CRISPR-Cas9 is a revolutionary gene-editing technology that offers the potential to treat diseases such as cancer, but the effects of CRISPR in patients are currently unknown. Stadtmauer et al. report a phase 1 clinical trial to assess the safety and feasibility of CRISPR-Cas9 gene editing in three patients with advanced cancer (see the Perspective by Hamilton and Doudna). They removed immune cells called T lymphocytes from patients and used CRISPR-Cas9 to disrupt three genes ( TRAC, TRBC , and PDCD1 ) with the goal of improving antitumor immunity. A cancer-targeting transgene, NY-ESO-1, was also introduced to recognize tumors. The engineered cells were administered to patients and were well tolerated, with durable engraftment observed for the study duration. These encouraging observations pave the way for future trials to study CRISPR-engineered cancer immunotherapies. Science , this issue p. eaba7365 ; see also p. 976

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