Determinants of response and resistance to CD19 chimeric antigen receptor (CAR) T cell therapy of chronic lymphocytic leukemia

• Published in: Nature medicine Vol. 24; no. 5; pp. 563 - 571
• Main Authors: Fraietta, Joseph A, Lacey, Simon F, Orlando, Elena J, Pruteanu-Malinici, Iulian, Gohil, Mercy, Lundh, Stefan, Boesteanu, Alina C, Wang, Yan, O'Connor, Roddy S, Hwang, Wei-Ting, Pequignot, Edward, Ambrose, David E, Zhang, Changfeng, Wilcox, Nicholas, Bedoya, Felipe, Dorfmeier, Corin, Chen, Fang, Tian, Lifeng, Parakandi, Harit, Gupta, Minnal, Young, Regina M, Johnson, F Brad, Kulikovskaya, Irina, Liu, Li, Xu, Jun, Kassim, Sadik H, Davis, Megan M, Levine, Bruce L, Frey, Noelle V, Siegel, Donald L, Huang, Alexander C, Wherry, E John, Bitter, Hans, Brogdon, Jennifer L, Porter, David L, June, Carl H, Melenhorst, J Joseph
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01.05.2018
• Subjects: Animals; Antigens; Antigens, CD19 - metabolism; Apoptosis; Autoantigens; Biomarkers; Cancer; CD19 antigen; CD27 antigen; CD8 antigen; Cell proliferation; Cell therapy; Chimeric antigen receptors; Chronic lymphocytic leukemia; Cytokines; Exhaustion; Female; Genomics; Glycolysis; Immunological memory; Immunological tolerance; Immunology; Immunotherapy; Immunotherapy, Adoptive; Interleukin 6; Interleukin 6 receptors; Interleukin-6 - metabolism; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell - immunology; Leukemia, Lymphocytic, Chronic, B-Cell - therapy; Lymphatic leukemia; Lymphocytes; Lymphocytes T; Male; Memory cells; Mice; Patients; PD-1 protein; Receptors; Receptors, Chimeric Antigen - metabolism; Remission; Stat3 protein; STAT3 Transcription Factor - metabolism; Transcription, Genetic; Treatment Outcome; Tumors

Tolerance to self-antigens prevents the elimination of cancer by the immune system . We used synthetic chimeric antigen receptors (CARs) to overcome immunological tolerance and mediate tumor rejection in patients with chronic lymphocytic leukemia (CLL). Remission was induced in a subset of subjects,...