PMID- 33512414
OWN - NLM
STAT- MEDLINE
DCOM- 20211206
LR  - 20240403
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 137
IP  - 17
DP  - 2021 Apr 29
TI  - CD22-directed CAR T-cell therapy induces complete remissions in CD19-directed 
      CAR-refractory large B-cell lymphoma.
PG  - 2321-2325
LID - 10.1182/blood.2020009432 [doi]
AB  - The prognosis of patients with large B-cell lymphoma (LBCL) that progresses after 
      treatment with chimeric antigen receptor (CAR) T-cell therapy targeting CD19 
      (CAR19) is poor. We report on the first 3 consecutive patients with autologous 
      CAR19-refractory LBCL who were treated with a single infusion of autologous 1 x 
      106 CAR+ T cells per kilogram targeting CD22 (CAR22) as part of a phase 1 
      dose-escalation study. CAR22 therapy was relatively well tolerated, without any 
      observed nonhematologic adverse events higher than grade 2. After infusion, all 3 
      patients achieved complete remission, with all responses continuing at the time 
      of last follow-up (mean, 7.8 months; range, 6-9.3). Circulating CAR22 cells 
      demonstrated robust expansion (peak range, 85.4-350 cells per microliter), and 
      persisted beyond 3 months in all patients with continued radiographic responses 
      and corresponding decreases in circulating tumor DNA beyond 6 months after 
      infusion. Further accrual at a higher dose level in this phase 1 dose-escalation 
      study is ongoing and will explore the role of this therapy in patients in whom 
      prior CAR T-cell therapies have failed. This trial is registered on 
      clinicaltrials.gov as #NCT04088890.
CI  - (c) 2021 by The American Society of Hematology.
FAU - Baird, John H
AU  - Baird JH
AD  - Division of Blood and Marrow Transplantation, Department of Medicine, Stanford 
      University School of Medicine, Stanford, CA.
AD  - Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, 
      Stanford, CA.
FAU - Frank, Matthew J
AU  - Frank MJ
AD  - Division of Blood and Marrow Transplantation, Department of Medicine, Stanford 
      University School of Medicine, Stanford, CA.
AD  - Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, 
      Stanford, CA.
FAU - Craig, Juliana
AU  - Craig J
AD  - Division of Blood and Marrow Transplantation, Department of Medicine, Stanford 
      University School of Medicine, Stanford, CA.
AD  - Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, 
      Stanford, CA.
FAU - Patel, Shabnum
AU  - Patel S
AD  - Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, 
      Stanford, CA.
FAU - Spiegel, Jay Y
AU  - Spiegel JY
AD  - Division of Blood and Marrow Transplantation, Department of Medicine, Stanford 
      University School of Medicine, Stanford, CA.
AD  - Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, 
      Stanford, CA.
FAU - Sahaf, Bita
AU  - Sahaf B
AD  - Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, 
      Stanford, CA.
FAU - Oak, Jean S
AU  - Oak JS
AD  - Department of Pathology.
FAU - Younes, Sheren F
AU  - Younes SF
AD  - Department of Pathology.
FAU - Ozawa, Michael G
AU  - Ozawa MG
AD  - Department of Pathology.
FAU - Yang, Eric
AU  - Yang E
AD  - Department of Pathology.
FAU - Natkunam, Yasodha
AU  - Natkunam Y
AD  - Department of Pathology.
FAU - Tamaresis, John
AU  - Tamaresis J
AD  - Department of Biomedical Data Science, and.
FAU - Ehlinger, Zachary
AU  - Ehlinger Z
AD  - Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, 
      Stanford, CA.
FAU - Reynolds, Warren D
AU  - Reynolds WD
AD  - Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, 
      Stanford, CA.
FAU - Arai, Sally
AU  - Arai S
AD  - Division of Blood and Marrow Transplantation, Department of Medicine, Stanford 
      University School of Medicine, Stanford, CA.
FAU - Johnston, Laura
AU  - Johnston L
AD  - Division of Blood and Marrow Transplantation, Department of Medicine, Stanford 
      University School of Medicine, Stanford, CA.
FAU - Lowsky, Robert
AU  - Lowsky R
AD  - Division of Blood and Marrow Transplantation, Department of Medicine, Stanford 
      University School of Medicine, Stanford, CA.
FAU - Meyer, Everett
AU  - Meyer E
AD  - Division of Blood and Marrow Transplantation, Department of Medicine, Stanford 
      University School of Medicine, Stanford, CA.
AD  - Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, 
      Stanford, CA.
FAU - Negrin, Robert S
AU  - Negrin RS
AD  - Division of Blood and Marrow Transplantation, Department of Medicine, Stanford 
      University School of Medicine, Stanford, CA.
FAU - Rezvani, Andrew R
AU  - Rezvani AR
AD  - Division of Blood and Marrow Transplantation, Department of Medicine, Stanford 
      University School of Medicine, Stanford, CA.
FAU - Shiraz, Parveen
AU  - Shiraz P
AD  - Division of Blood and Marrow Transplantation, Department of Medicine, Stanford 
      University School of Medicine, Stanford, CA.
AD  - Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, 
      Stanford, CA.
FAU - Sidana, Surbhi
AU  - Sidana S
AD  - Division of Blood and Marrow Transplantation, Department of Medicine, Stanford 
      University School of Medicine, Stanford, CA.
AD  - Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, 
      Stanford, CA.
FAU - Weng, Wen-Kai
AU  - Weng WK
AD  - Division of Blood and Marrow Transplantation, Department of Medicine, Stanford 
      University School of Medicine, Stanford, CA.
FAU - Davis, Kara L
AU  - Davis KL
AD  - Division of Hematology/Oncology, Department of Pediatrics, Stanford University 
      School of Medicine, Stanford, CA; and.
FAU - Ramakrishna, Sneha
AU  - Ramakrishna S
AD  - Division of Hematology/Oncology, Department of Pediatrics, Stanford University 
      School of Medicine, Stanford, CA; and.
FAU - Schultz, Liora
AU  - Schultz L
AD  - Division of Hematology/Oncology, Department of Pediatrics, Stanford University 
      School of Medicine, Stanford, CA; and.
FAU - Mullins, Chelsea
AU  - Mullins C
AD  - Adaptive Biotechnologies, Seattle, WA.
FAU - Jacob, Allison
AU  - Jacob A
AD  - Adaptive Biotechnologies, Seattle, WA.
FAU - Kirsch, Ilan
AU  - Kirsch I
AD  - Adaptive Biotechnologies, Seattle, WA.
FAU - Feldman, Steven A
AU  - Feldman SA
AD  - Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, 
      Stanford, CA.
FAU - Mackall, Crystal L
AU  - Mackall CL
AD  - Division of Blood and Marrow Transplantation, Department of Medicine, Stanford 
      University School of Medicine, Stanford, CA.
AD  - Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, 
      Stanford, CA.
AD  - Division of Hematology/Oncology, Department of Pediatrics, Stanford University 
      School of Medicine, Stanford, CA; and.
FAU - Miklos, David B
AU  - Miklos DB
AD  - Division of Blood and Marrow Transplantation, Department of Medicine, Stanford 
      University School of Medicine, Stanford, CA.
AD  - Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, 
      Stanford, CA.
FAU - Muffly, Lori
AU  - Muffly L
AD  - Division of Blood and Marrow Transplantation, Department of Medicine, Stanford 
      University School of Medicine, Stanford, CA.
AD  - Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, 
      Stanford, CA.
LA  - eng
SI  - ClinicalTrials.gov/NCT04088890
GR  - K08 CA248968/CA/NCI NIH HHS/United States
GR  - KL2 TR003143/TR/NCATS NIH HHS/United States
GR  - P01 CA049605/CA/NCI NIH HHS/United States
GR  - P30 CA124435/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Antigens, CD19)
RN  - 0 (CD22 protein, human)
RN  - 0 (Sialic Acid Binding Ig-like Lectin 2)
SB  - IM
MH  - Antigens, CD19/*immunology
MH  - Clinical Trials, Phase I as Topic
MH  - Humans
MH  - Immunotherapy, Adoptive/*methods
MH  - Lymphoma, Large B-Cell, Diffuse/immunology/pathology/*therapy
MH  - Prognosis
MH  - Remission Induction
MH  - Sialic Acid Binding Ig-like Lectin 2/*immunology
PMC - PMC8085484
COIS- Conflict-of-interest disclosure: P.S. has received research support from Kite 
      Pharma-Gilead. A.R.R. has received research support from Pharmacyclics/AbbVie, 
      served on 1-time ad hoc scientific advisory boards of Nohla Therapeutics and 
      Kaleido, and was an expert witness for the U.S. Department of Justice. His 
      brother works for Johnson & Johnson. C.L.M. has consulted for Lyell, Neoimmune 
      Tech, Nektar, and Apricity; has received royalties from NIH and Juno Therapeutics 
      for CD22-CAR; holds equity in Lyell and Apricity; and has received research 
      support from Lyell. D.B.M. has consulted for Kite Pharma-Gilead, Juno 
      Therapeutics-Celgene, Novartis, Janssen, and Pharmacyclics and has received 
      research support from Kite Pharma-Gilead, Allogene, Pharmacyclics, Miltenyi 
      Biotec, and Adaptive Biotechnologies. S.S. has consulted for Janssen. C.M., A.J., 
      and I.K. are full-time employees of Adaptive Biotechnologies. S.A.F. has 
      consulted for Lonza PerMed, Gradalis, Obsidian, and Samsara BioCapital; L.M. has 
      received research support from Adaptive Biotechnologies and Servier Laboratories 
      and has consulted for Amgen and Pfizer. The remaining authors declare no 
      competing financial interests.
EDAT- 2021/01/30 06:00
MHDA- 2021/12/15 06:00
PMCR- 2022/04/29
CRDT- 2021/01/29 12:13
PHST- 2020/10/06 00:00 [received]
PHST- 2020/11/24 00:00 [accepted]
PHST- 2021/01/30 06:00 [pubmed]
PHST- 2021/12/15 06:00 [medline]
PHST- 2021/01/29 12:13 [entrez]
PHST- 2022/04/29 00:00 [pmc-release]
AID - S0006-4971(20)86027-3 [pii]
AID - 2021/BLD2020009432 [pii]
AID - 10.1182/blood.2020009432 [doi]
PST - ppublish
SO  - Blood. 2021 Apr 29;137(17):2321-2325. doi: 10.1182/blood.2020009432.