PMID- 37933565
OWN - NLM
STAT- MEDLINE
DCOM- 20231226
LR  - 20240517
IS  - 1029-2403 (Electronic)
IS  - 1026-8022 (Linking)
VI  - 64
IP  - 14
DP  - 2023 Dec
TI  - Functional drivers of resistance to anti-CD19 CAR-T cell therapy in diffuse large 
      B cell lymphoma.
PG  - 2217-2224
LID - 10.1080/10428194.2023.2258244 [doi]
AB  - Chimeric antigen receptor T-cell therapy targeting CD19 (CAR-19) promotes 
      impressive durable remissions for relapsed or refractory (rel/ref) large B-cell 
      lymphoma (LBCL) patients with historically poor prognoses. Despite this, over 
      half of patients still fail to respond or eventually progress. Studies to reveal 
      mechanisms of resistance have examined host clinical parameters, CAR-19 product 
      composition, and tumor microenvironment (TME) alterations, while a relative 
      paucity of studies has analyzed contributions by genomic alterations in tumor 
      cells. Factors associated with outcome include increased tumor volume, specific 
      characteristics of infused CAR-T products, infiltration by myeloid cells in tumor 
      microenvironments, and markers of complexity in LBCL genomes. Functional 
      laboratory studies of resistance are largely absent in the current literature, 
      illustrating a need for experiments in genetically accurate immunocompetent 
      systems to confirm candidate alterations' roles in resistance and inform future 
      improvements. In this review, we highlight key studies that have elucidated 
      biomarkers of resistance in hosts, CAR products, TMEs, and comparatively 
      understudied tumor-intrinsic mediators encoded by tumor genomes. We conclude with 
      an experimental framework suitable for CAR-19 resistance biomarker identification 
      and laboratory functional validation.
FAU - Newsam, Austin D
AU  - Newsam AD
AD  - Medical Scientist Training Program, University of Miami Miller School of 
      Medicine, Miami, FL, USA.
AD  - Sheila and David Fuente Graduate Program in Cancer Biology, University of Miami 
      Miller School of Medicine, Miami, FL, USA.
AD  - Sylvester Comprehensive Cancer Center, University of Miami Miller School of 
      Medicine, Miami, FL, USA.
FAU - Coughlin, Caroline A
AU  - Coughlin CA
AD  - Medical Scientist Training Program, University of Miami Miller School of 
      Medicine, Miami, FL, USA.
AD  - Sheila and David Fuente Graduate Program in Cancer Biology, University of Miami 
      Miller School of Medicine, Miami, FL, USA.
AD  - Sylvester Comprehensive Cancer Center, University of Miami Miller School of 
      Medicine, Miami, FL, USA.
FAU - Trabolsi, Asaad
AU  - Trabolsi A
AD  - Sylvester Comprehensive Cancer Center, University of Miami Miller School of 
      Medicine, Miami, FL, USA.
AD  - Hematology-Oncology Fellowship Training Program, Jackson Memorial Hospital, 
      Miami, FL, USA.
FAU - Schatz, Jonathan H
AU  - Schatz JH
AD  - Sylvester Comprehensive Cancer Center, University of Miami Miller School of 
      Medicine, Miami, FL, USA.
AD  - Division of Hematology, Department of Medicine, University of Miami Miller School 
      of Medicine, Miami, FL, USA.
LA  - eng
GR  - F30 CA265106/CA/NCI NIH HHS/United States
GR  - P30 CA240139/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Review
DEP - 20231225
PL  - United States
TA  - Leuk Lymphoma
JT  - Leukemia & lymphoma
JID - 9007422
RN  - 0 (Receptors, Chimeric Antigen)
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - 0 (Antigens, CD19)
SB  - IM
MH  - Humans
MH  - *Receptors, Chimeric Antigen
MH  - Receptors, Antigen, T-Cell/genetics
MH  - T-Lymphocytes
MH  - *Lymphoma, Large B-Cell, Diffuse/therapy/drug therapy
MH  - Immunotherapy, Adoptive
MH  - Antigens, CD19
MH  - Cell- and Tissue-Based Therapy
MH  - Tumor Microenvironment
OTO - NOTNLM
OT  - CAR-T
OT  - lymphoma
OT  - mechanisms
OT  - resistance
EDAT- 2023/11/07 06:46
MHDA- 2023/12/26 06:42
CRDT- 2023/11/07 05:27
PHST- 2023/12/26 06:42 [medline]
PHST- 2023/11/07 06:46 [pubmed]
PHST- 2023/11/07 05:27 [entrez]
AID - 10.1080/10428194.2023.2258244 [doi]
PST - ppublish
SO  - Leuk Lymphoma. 2023 Dec;64(14):2217-2224. doi: 10.1080/10428194.2023.2258244. 
      Epub 2023 Dec 25.