Immune determinants of CAR-T cell expansion in solid tumor patients receiving GD2 CAR-T cell therapy.
Chimeric antigen receptor T cells (CAR-Ts) have remarkable efficacy in liquid tumors, but limited responses in solid tumors. We conducted a Phase I trial (NCT02107963) of GD2 CAR-Ts (GD2-CAR.OX40.28.z.iC9), demonstrating feasibility and safety of administration in children and young adults with osteosarcoma and neuroblastoma. Since CAR-T efficacy requires adequate CAR-T expansion, patients were grouped into good or poor expanders across dose levels. Patient samples were evaluated by multi-dimensional proteomic, transcriptomic, and epigenetic analyses. T cell assessments identified naive T cells in pre-treatment apheresis associated with good expansion, and exhausted T cells in CAR-T products with poor expansion. Myeloid cell assessment identified CXCR3+ monocytes in pre-treatment apheresis associated with good expansion. Longitudinal analysis of post-treatment samples identified increased CXCR3- classical monocytes in all groups as CAR-T numbers waned. Together, our data uncover mediators of CAR-T biology and correlates of expansion that could be utilized to advance immunotherapies for solid tumor patients.
Pubmed ID: 38134936 RIS Download
Research resources used in this publication
None foundAdditional research tools detected in this publication
None foundAntibodies used in this publication
- Anti-Human CD16 (3G8)-209Bi—100 Tests (RRID:AB_2756431)
- Anti-Human CD279/PD-1 (EH12.2H7)-174Yb (RRID:AB_2868402)
- EOMES Monoclonal Antibody (WD1928), eBioscience (RRID:AB_2572882)
- Hydrocodone Polyclonal Antibody (RRID:AB_1090063)
- Purified anti-human CD95 (Fas) (Maxpar(R) Ready) (RRID:AB_2563766)
- Purified anti-human CD122 (IL-2Rbeta) (Maxpar(R) Ready) (RRID:AB_2563712)
- polyclonal anti-Clostridium botulinum D Toxoid (RRID:AB_1066238)
- Anti-Human CD45RA (HI100)-170Er (RRID:AB_2938862)
- Anti-Human CD366/Tim-3 (F38-2E2) - 169Tm (RRID:AB_2905650)
- Anti-Human CD127/IL-7Ra (A019D5)-168Er—100 Tests (RRID:AB_2756425)
- Purified anti-human CD160 (RRID:AB_2074411)
- Anti-Human CD223-165Ho Antibody (RRID:AB_2687859)
- Purified anti-human CD39 (Maxpar(R) Ready) (RRID:AB_2563747)
- Anti-Human CD272/BTLA (MIH26)-163Dy (RRID:AB_2910546)
- Purified anti-human CD25 (RRID:AB_2561751)
- Anti-Human CD152/CTLA-4 (14D3) Antibody (RRID:AB_2687649)
- Anti-Human/Mouse Tbet (4B10)-160Gd (RRID:AB_2810251)
- Purified anti-human CD20 (RRID:AB_314250)
- Anti-Human CD137/4-1BB (4B4-1)-158Gd (RRID:AB_2888927)
- Purified anti-Cleaved PARP (Asp214) Recombinant (RRID:AB_2814517)
- Anti-Human TIGIT (MBSA43)-153Eu—100 Tests (RRID:AB_2756419)
- Purified anti-human CD38 (Maxpar(R) Ready) (RRID:AB_2562819)
- Purified anti-human CD244 (2B4) (RRID:AB_1279194)
- Anti-Human CD134/OX40 (ACT35)-150Nd (RRID:AB_2938869)
- Anti-Human CD45RO (UCHL1)-149Sm Antibody (RRID:AB_2687851)
- Anti-Human CD274/PDL1 (29E.2A3) Antibody (RRID:AB_2687638)
- Purified anti-human CD28 (Maxpar(R) Ready) (RRID:AB_2563737)
- Anti-Human CD8 (RPA-T8) Antibody (RRID:AB_2687641)
- Anti-Human CD4 (RPA-T4)-145Nd (RRID:AB_2661789)
- Anti-Human CD11b/Mac-1 (ICRF44)-144Nd (RRID:AB_2714152)
- Purified anti-human CD57 (MaxPar® Ready) (RRID:AB_2563757)
- Purified anti-human CD27 (Maxpar(R) Ready) (RRID:AB_2562817)
- Anti-Human CD45 (HI30)-89Y (RRID:AB_2938863)
- Purified anti-human CD3 (RRID:AB_314056)
- PE anti-human CD66b (RRID:AB_2750201)
- APC anti-human Lineage Cocktail (CD3, CD19, CD20, CD56) (RRID:AB_2916117)
- Slan (M-DC8) Antibody, anti-human, FITC (RRID:AB_2733608)
- Brilliant Violet 650(TM) anti-human CD3 (RRID:AB_2629574)
- PE anti-human CD183 (CXCR3) (RRID:AB_10962912)
- Brilliant Violet 421(TM) anti-human HLA-DR (RRID:AB_2561831)
- APC/Cyanine7 anti-human CD16 (RRID:AB_2562952)
- APC anti-human CD15 (SSEA-1) (RRID:AB_756014)
- Brilliant Violet 605(TM) anti-human CD33 (RRID:AB_2566405)
- Brilliant Violet 711(TM) anti-human CD14 (RRID:AB_2814323)
- Brilliant Violet 785(TM) anti-mouse/human CD11b (RRID:AB_2561373)
- Brilliant Violet 711(TM) anti-human CD25 (RRID:AB_2632781)
- CD62L (L-Selectin) (RRID:AB_2744441)
- Rabbit Anti-Yeast Rpn12 Antibody, Unconjugated (RRID:AB_1056167)
- Brilliant Violet 421(TM) anti-human CD95 (Fas) (RRID:AB_2561830)
- APC anti-human CD4 (RRID:AB_2820224)
- PE anti-human CD8 (RRID:AB_2616623)
- Brilliant Violet 785(TM) anti-human CD3 (RRID:AB_2687178)
- PerCP/Cyanine5.5 anti-human CD45 (RRID:AB_893338)
- Anti-Human CD11b/Mac-1 (ICRF44) Antibody (RRID:AB_2687654)
- Anti-Human CD56 (NCAM16.2)-176Yb (RRID:AB_2938870)
- Purified anti-human CD10 (RRID:AB_314913)
- Purified anti-human CD169 (Sialoadhesin, Siglec-1) (RRID:AB_2189031)
- Anti-Human Ki-67-172Yb (RRID:AB_2858243)
- Purified anti-human CD141 (Thrombomodulin) (RRID:AB_2201808)
- Anti-Human CD9 (SN4 C3-3A2)-171Yb (RRID:AB_2877094)
- Anti-Human CD152/CTLA-4 (14D3)-170Er (RRID:AB_2858238)
- Anti-Slan (M-DC8)-FITC, human (RRID:AB_2660075)
- Purified anti-human Lymphotoxin beta Receptor (LT-betaR) (RRID:AB_2139071)
- Anti-Human CD197/CCR7 (G043H7)-167Er (RRID:AB_2858236)
- Purified anti-human CD279 (PD-1) (RRID:AB_940488)
- Anti-Human CD16 (3G8)-165Ho (RRID:AB_2802109)
- Anti-Human CD15/SSEA-1 (W6D3)-164Dy (RRID:AB_2810970)
- Anti-Human CD33 (WM53)-163Dy Antibody (RRID:AB_2687857)
- Purified anti-human CD273 (B7-DC, PD-L2) (RRID:AB_1953319)
- Ultra-LEAF(TM) Purified anti-human CD253 (Trail) (RRID:AB_2814154)
- Anti-Human CD14 (M5E2) Antibody (RRID:AB_2687634)
- Anti-Human CD357 (621)-159Tb (RRID:AB_2858232)
- Anti-Human CD183/CXCR3 (G025H7) Antibody (RRID:AB_2687646)
- Anti-Human CD33 (WM53)-158Gd (RRID:AB_2661799)
- Anti-Human CD36 (5-271)-155Gd (RRID:AB_2756286)
- Purified anti-human CD142 (RRID:AB_2564564)
- Anti-Human CD66b (80H3)-152Sm (RRID:AB_2661795)
- Anti-Human CD103 (Ber-ACT8)-151Eu—100 Tests (RRID:AB_2756418)
- Purified anti-human CD206 (MMR) (RRID:AB_571923)
- Purified anti-human CD45RA (Maxpar(R) Ready) (RRID:AB_2562822)
- Purified anti-human CD3 (RRID:AB_571927)
- Anti-Human CD69 (FN50)-144Nd Antibody (RRID:AB_2687849)
- Anti-Human CD123-143Nd (RRID:AB_2811081)
- Anti-Human CD19 (HIB19)-142Nd (RRID:AB_2651155)
- Purified anti-human CD1c (RRID:AB_1088996)
- Purified anti-human CD235ab (RRID:AB_314620)
- Purified anti-human CD41 (RRID:AB_314372)
- Purified anti-human CD45 (RRID:AB_314390)
- Purified anti-human HLA-DR (RRID:AB_314680)
Associated grants
- Agency: NCI NIH HHS, United States
Id: U01 CA224766 - Agency: NIGMS NIH HHS, United States
Id: T32 GM007365 - Agency: NCI NIH HHS, United States
Id: F30 CA271797 - Agency: Intramural NIH HHS, United States
Id: ZIA BC011334 - Agency: NCI NIH HHS, United States
Id: U24 CA224316 - Agency: NCI NIH HHS, United States
Id: K08 CA267057 - Agency: NCI NIH HHS, United States
Id: U24 CA224331 - Agency: NCI NIH HHS, United States
Id: R01 CA202987 - Agency: Intramural NIH HHS, United States
Id: ZIA BC011332 - Agency: NCI NIH HHS, United States
Id: U24 CA224309
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
This is a list of tools and resources that we have found mentioned in this publication.
Anti-Human CD16 (3G8)-209Bi—100 Tests (antibody)
RRID:AB_2756431
This monoclonal targets CD16
View all literature mentionsAnti-Human CD279/PD-1 (EH12.2H7)-174Yb (antibody)
RRID:AB_2868402
This monoclonal targets CD279/PD-1
View all literature mentionsEOMES Monoclonal Antibody (WD1928), eBioscience (antibody)
RRID:AB_2572882
This monoclonal targets EOMES
View all literature mentionsHydrocodone Polyclonal Antibody (antibody)
RRID:AB_1090063
This unknown targets Hydrocodone
View all literature mentionsPurified anti-human CD95 (Fas) (Maxpar(R) Ready) (antibody)
RRID:AB_2563766
This monoclonal targets CD95
View all literature mentionsPurified anti-human CD122 (IL-2Rbeta) (Maxpar(R) Ready) (antibody)
RRID:AB_2563712
This monoclonal targets CD122
View all literature mentionspolyclonal anti-Clostridium botulinum D Toxoid (antibody)
RRID:AB_1066238
This polyclonal targets polyclonal anti-Clostridium botulinum D Toxoid
View all literature mentionsAnti-Human CD45RA (HI100)-170Er (antibody)
RRID:AB_2938862
This monoclonal targets CD45RA
View all literature mentionsAnti-Human CD366/Tim-3 (F38-2E2) - 169Tm (antibody)
RRID:AB_2905650
This monoclonal targets TIM-3
View all literature mentionsAnti-Human CD127/IL-7Ra (A019D5)-168Er—100 Tests (antibody)
RRID:AB_2756425
This monoclonal targets CD127/IL-7Ra
View all literature mentionsPurified anti-human CD160 (antibody)
RRID:AB_2074411
This monoclonal targets CD160
View all literature mentionsAnti-Human CD223-165Ho Antibody (antibody)
RRID:AB_2687859
This monoclonal targets CD223
View all literature mentionsPurified anti-human CD39 (Maxpar(R) Ready) (antibody)
RRID:AB_2563747
This monoclonal targets CD39
View all literature mentionsAnti-Human CD272/BTLA (MIH26)-163Dy (antibody)
RRID:AB_2910546
This monoclonal targets CD272/BTLA
View all literature mentionsPurified anti-human CD25 (antibody)
RRID:AB_2561751
This monoclonal targets CD25
View all literature mentionsAnti-Human CD152/CTLA-4 (14D3) Antibody (antibody)
RRID:AB_2687649
This monoclonal targets CD152/CTLA-4
View all literature mentionsAnti-Human/Mouse Tbet (4B10)-160Gd (antibody)
RRID:AB_2810251
This monoclonal targets Tbet
View all literature mentionsPurified anti-human CD20 (antibody)
RRID:AB_314250
This monoclonal targets CD20
View all literature mentionsAnti-Human CD137/4-1BB (4B4-1)-158Gd (antibody)
RRID:AB_2888927
This monoclonal targets CD137/4-1BB
View all literature mentionsPurified anti-Cleaved PARP (Asp214) Recombinant (antibody)
RRID:AB_2814517
This recombinant monoclonal targets Cleaved PARP
View all literature mentionsAnti-Human TIGIT (MBSA43)-153Eu—100 Tests (antibody)
RRID:AB_2756419
This monoclonal targets TIGIT
View all literature mentionsPurified anti-human CD38 (Maxpar(R) Ready) (antibody)
RRID:AB_2562819
This monoclonal targets CD38
View all literature mentionsPurified anti-human CD244 (2B4) (antibody)
RRID:AB_1279194
This monoclonal targets CD244
View all literature mentionsAnti-Human CD134/OX40 (ACT35)-150Nd (antibody)
RRID:AB_2938869
This monoclonal targets CD134/OX40
View all literature mentionsAnti-Human CD45RO (UCHL1)-149Sm Antibody (antibody)
RRID:AB_2687851
This monoclonal targets CD45RO
View all literature mentionsAnti-Human CD274/PDL1 (29E.2A3) Antibody (antibody)
RRID:AB_2687638
This monoclonal targets CD274/PDL1
View all literature mentionsPurified anti-human CD28 (Maxpar(R) Ready) (antibody)
RRID:AB_2563737
This monoclonal targets CD28
View all literature mentionsAnti-Human CD8 (RPA-T8) Antibody (antibody)
RRID:AB_2687641
This monoclonal targets CD8
View all literature mentionsAnti-Human CD4 (RPA-T4)-145Nd (antibody)
RRID:AB_2661789
This unknown targets
View all literature mentionsAnti-Human CD11b/Mac-1 (ICRF44)-144Nd (antibody)
RRID:AB_2714152
This monoclonal targets CD11b
View all literature mentionsPurified anti-human CD57 (MaxPar® Ready) (antibody)
RRID:AB_2563757
This monoclonal targets CD57
View all literature mentionsPurified anti-human CD27 (Maxpar(R) Ready) (antibody)
RRID:AB_2562817
This monoclonal targets CD27
View all literature mentionsAnti-Human CD45 (HI30)-89Y (antibody)
RRID:AB_2938863
This monoclonal targets CD45
View all literature mentionsPurified anti-human CD3 (antibody)
RRID:AB_314056
This monoclonal targets CD3
View all literature mentionsPE anti-human CD66b (antibody)
RRID:AB_2750201
This monoclonal targets CD66b
View all literature mentionsAPC anti-human Lineage Cocktail (CD3, CD19, CD20, CD56) (antibody)
RRID:AB_2916117
This cocktail targets CD3, CD19, CD20, CD56
View all literature mentionsSlan (M-DC8) Antibody, anti-human, FITC (antibody)
RRID:AB_2733608
This monoclonal targets Slan (M-DC8)
View all literature mentionsBrilliant Violet 650(TM) anti-human CD3 (antibody)
RRID:AB_2629574
This monoclonal targets CD3
View all literature mentionsPE anti-human CD183 (CXCR3) (antibody)
RRID:AB_10962912
This monoclonal targets CD183
View all literature mentionsBrilliant Violet 421(TM) anti-human HLA-DR (antibody)
RRID:AB_2561831
This monoclonal targets HLA-DR
View all literature mentionsAPC/Cyanine7 anti-human CD16 (antibody)
RRID:AB_2562952
This monoclonal targets CD16
View all literature mentionsAPC anti-human CD15 (SSEA-1) (antibody)
RRID:AB_756014
This monoclonal targets CD15
View all literature mentionsBrilliant Violet 605(TM) anti-human CD33 (antibody)
RRID:AB_2566405
This monoclonal targets CD33
View all literature mentionsBrilliant Violet 711(TM) anti-human CD14 (antibody)
RRID:AB_2814323
This monoclonal targets CD14
View all literature mentionsBrilliant Violet 785(TM) anti-mouse/human CD11b (antibody)
RRID:AB_2561373
This monoclonal targets CD11b
View all literature mentionsBrilliant Violet 711(TM) anti-human CD25 (antibody)
RRID:AB_2632781
This monoclonal targets CD25
View all literature mentionsCD62L (L-Selectin) (antibody)
RRID:AB_2744441
This monoclonal targets CD62L (L-Selectin)
View all literature mentionsRabbit Anti-Yeast Rpn12 Antibody, Unconjugated (antibody)
RRID:AB_1056167
This unknown targets Yeast Rpn12
View all literature mentionsBrilliant Violet 421(TM) anti-human CD95 (Fas) (antibody)
RRID:AB_2561830
This monoclonal targets CD95
View all literature mentionsAPC anti-human CD4 (antibody)
RRID:AB_2820224
This monoclonal targets CD4
View all literature mentionsPE anti-human CD8 (antibody)
RRID:AB_2616623
This monoclonal targets CD8
View all literature mentionsBrilliant Violet 785(TM) anti-human CD3 (antibody)
RRID:AB_2687178
This monoclonal targets CD3
View all literature mentionsPerCP/Cyanine5.5 anti-human CD45 (antibody)
RRID:AB_893338
This monoclonal targets CD45
View all literature mentionsAnti-Human CD11b/Mac-1 (ICRF44) Antibody (antibody)
RRID:AB_2687654
This monoclonal targets CD11b/Mac-1
View all literature mentionsAnti-Human CD56 (NCAM16.2)-176Yb (antibody)
RRID:AB_2938870
This monoclonal targets CD56
View all literature mentionsPurified anti-human CD10 (antibody)
RRID:AB_314913
This monoclonal targets CD10
View all literature mentionsPurified anti-human CD169 (Sialoadhesin, Siglec-1) (antibody)
RRID:AB_2189031
This monoclonal targets CD169
View all literature mentionsAnti-Human Ki-67-172Yb (antibody)
RRID:AB_2858243
This monoclonal targets Ki67
View all literature mentionsPurified anti-human CD141 (Thrombomodulin) (antibody)
RRID:AB_2201808
This monoclonal targets CD141
View all literature mentionsAnti-Human CD9 (SN4 C3-3A2)-171Yb (antibody)
RRID:AB_2877094
This monoclonal targets CD9
View all literature mentionsAnti-Human CD152/CTLA-4 (14D3)-170Er (antibody)
RRID:AB_2858238
This monoclonal targets CD152/CTLA-4
View all literature mentionsAnti-Slan (M-DC8)-FITC, human (antibody)
RRID:AB_2660075
This monoclonal targets Slan (M-DC8)
View all literature mentionsPurified anti-human Lymphotoxin beta Receptor (LT-betaR) (antibody)
RRID:AB_2139071
This monoclonal targets LT-betaR
View all literature mentionsAnti-Human CD197/CCR7 (G043H7)-167Er (antibody)
RRID:AB_2858236
This monoclonal targets CD197/CCR7
View all literature mentionsPurified anti-human CD279 (PD-1) (antibody)
RRID:AB_940488
This monoclonal targets CD279
View all literature mentionsAnti-Human CD16 (3G8)-165Ho (antibody)
RRID:AB_2802109
This monoclonal targets CD16
View all literature mentionsAnti-Human CD15/SSEA-1 (W6D3)-164Dy (antibody)
RRID:AB_2810970
This monoclonal targets CD15/SSEA-1
View all literature mentionsAnti-Human CD33 (WM53)-163Dy Antibody (antibody)
RRID:AB_2687857
This monoclonal targets CD33
View all literature mentionsPurified anti-human CD273 (B7-DC, PD-L2) (antibody)
RRID:AB_1953319
This monoclonal targets CD273
View all literature mentionsUltra-LEAF(TM) Purified anti-human CD253 (Trail) (antibody)
RRID:AB_2814154
This monoclonal targets CD253
View all literature mentionsAnti-Human CD14 (M5E2) Antibody (antibody)
RRID:AB_2687634
This monoclonal targets CD14
View all literature mentionsAnti-Human CD357 (621)-159Tb (antibody)
RRID:AB_2858232
This monoclonal targets CD357 (GITR)
View all literature mentionsAnti-Human CD183/CXCR3 (G025H7) Antibody (antibody)
RRID:AB_2687646
This monoclonal targets CD183/CXCR3
View all literature mentionsAnti-Human CD33 (WM53)-158Gd (antibody)
RRID:AB_2661799
This unknown targets CD33
View all literature mentionsAnti-Human CD36 (5-271)-155Gd (antibody)
RRID:AB_2756286
This monoclonal targets CD36
View all literature mentionsPurified anti-human CD142 (antibody)
RRID:AB_2564564
This monoclonal targets CD142
View all literature mentionsAnti-Human CD66b (80H3)-152Sm (antibody)
RRID:AB_2661795
This unknown targets CD66b
View all literature mentionsAnti-Human CD103 (Ber-ACT8)-151Eu—100 Tests (antibody)
RRID:AB_2756418
This monoclonal targets CD103
View all literature mentionsPurified anti-human CD206 (MMR) (antibody)
RRID:AB_571923
This monoclonal targets CD206
View all literature mentionsPurified anti-human CD45RA (Maxpar(R) Ready) (antibody)
RRID:AB_2562822
This monoclonal targets CD45RA
View all literature mentionsPurified anti-human CD3 (antibody)
RRID:AB_571927
This monoclonal targets CD3
View all literature mentionsAnti-Human CD69 (FN50)-144Nd Antibody (antibody)
RRID:AB_2687849
This monoclonal targets CD69
View all literature mentionsAnti-Human CD123-143Nd (antibody)
RRID:AB_2811081
This monoclonal targets CD123
View all literature mentionsAnti-Human CD19 (HIB19)-142Nd (antibody)
RRID:AB_2651155
This monoclonal targets CD19
View all literature mentionsPurified anti-human CD1c (antibody)
RRID:AB_1088996
This monoclonal targets CD1c
View all literature mentionsPurified anti-human CD235ab (antibody)
RRID:AB_314620
This monoclonal targets CD235ab
View all literature mentionsPurified anti-human CD41 (antibody)
RRID:AB_314372
This monoclonal targets CD41
View all literature mentionsPurified anti-human CD45 (antibody)
RRID:AB_314390
This monoclonal targets CD45
View all literature mentionsPurified anti-human HLA-DR (antibody)
RRID:AB_314680
This monoclonal targets HLA-DR
View all literature mentions
