Xiaojuan Chen1, Ying Wang1, Min Ruan1, Jun Li1, Mengjun Zhong1, Zhanqi Li1, Fang Liu1, Shuchun Wang1, Yumei Chen1, Lipeng Liu1, Jun J Yang2, Xiaofan Zhu1, Jianxiang Wang1, Ching-Hon Pui3. 1. State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Division of Pediatric Blood Disease Center, Institute of Hematology & Blood Disease Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China. 2. St. Jude Children's Research Hospital, Memphis, TN. 3. St. Jude Children's Research Hospital, Memphis, TN. Electronic address: ching-hon.pui@stjude.org.
Abstract
BACKGROUND: Irradiation has been a standard treatment for testicular relapse but is associated with severe hypogonadism. Because CD19-specific chimeric antigen receptor T (CAR-T) cells can eradicate leukemic blasts in cerebrospinal fluid, a pharmacologic sanctuary site, we tested the efficacy of this therapy in 7 boys with isolated testicular relapse of B-cell acute lymphoblastic leukemia. PATIENTS AND METHODS: CD19-specific CAR-T cells were generated with the use of autologous T cells transduced with a lentiviral vector to express a CAR molecule containing anti-CD19 scFv derived from the HI19α murine monoclonal antibody, human CD8α hinge, and human 4-1BB (CD137) and CD3ζ costimulatory signaling transmembrane domains. After the conditioning regimen, which consisted of intravenous fludarabine and intravenous cyclophosphamide, 7 patients with a median age of 9 years (range, 2-10 years) with isolated testicular relapse received a single infusion of CD19 CAR-T cells at a total dose of 5 × 106 all T cells per kilogram. RESULTS: All 7 patients achieved complete remission with normal testes. Six patients remained in second remission for 5 to 23 months (median, 14 months), and 1 patient subsequently relapsed in the bone marrow. The probability of event-free survival for all patients at 12 months of follow-up was 83.3% ± 15.2% (standard error). The treatment was well-tolerated, with grade 1 cytokine-release syndrome developing in 5 patients. CONCLUSION: These results suggest that CAR-T cell therapy is a treatment option for patients with testicular relapse.
BACKGROUND: Irradiation has been a standard treatment for testicular relapse but is associated with severe hypogonadism. Because CD19-specific chimeric antigen receptor T (CAR-T) cells can eradicate leukemic blasts in cerebrospinal fluid, a pharmacologic sanctuary site, we tested the efficacy of this therapy in 7 boys with isolated testicular relapse of B-cell acute lymphoblastic leukemia. PATIENTS AND METHODS: CD19-specific CAR-T cells were generated with the use of autologous T cells transduced with a lentiviral vector to express a CAR molecule containing anti-CD19scFv derived from the HI19α murine monoclonal antibody, human CD8α hinge, and human4-1BB (CD137) and CD3ζ costimulatory signaling transmembrane domains. After the conditioning regimen, which consisted of intravenous fludarabine and intravenous cyclophosphamide, 7 patients with a median age of 9 years (range, 2-10 years) with isolated testicular relapse received a single infusion of CD19CAR-T cells at a total dose of 5 × 106 all T cells per kilogram. RESULTS: All 7 patients achieved complete remission with normal testes. Six patients remained in second remission for 5 to 23 months (median, 14 months), and 1 patient subsequently relapsed in the bone marrow. The probability of event-free survival for all patients at 12 months of follow-up was 83.3% ± 15.2% (standard error). The treatment was well-tolerated, with grade 1 cytokine-release syndrome developing in 5 patients. CONCLUSION: These results suggest that CAR-T cell therapy is a treatment option for patients with testicular relapse.
Authors: Siennah R Miller; Joseph L Jilek; Meghan E McGrath; Raymond K Hau; Erin Q Jennings; James J Galligan; Stephen H Wright; Nathan J Cherrington Journal: Pharmacol Res Perspect Date: 2021-08
Authors: Semjon Willier; Johannes Raedler; Franziska Blaeschke; Dana Stenger; Montserrat Pazos Escudero; Florian Jurgeleit; Thomas G P Grünewald; Vera Binder; Irene Schmid; Michael H Albert; Armin Wolf; Tobias Feuchtinger Journal: J Immunother Cancer Date: 2020-09 Impact factor: 13.751