PMID- 21948234
OWN - NLM
STAT- MEDLINE
DCOM- 20120120
LR  - 20240510
IS  - 1557-3265 (Electronic)
IS  - 1078-0432 (Print)
IS  - 1078-0432 (Linking)
VI  - 17
IP  - 21
DP  - 2011 Nov 1
TI  - Phase I trial of adoptive cell transfer with mixed-profile type-I/type-II 
      allogeneic T cells for metastatic breast cancer.
PG  - 6878-87
LID - 10.1158/1078-0432.CCR-11-1579 [doi]
AB  - PURPOSE: Metastatic breast cancer (MBC) response to allogeneic lymphocytes 
      requires donor T-cell engraftment and is limited by graft-versus-host disease 
      (GVHD). In mice, type-II-polarized T cells promote engraftment and modulate GVHD, 
      whereas type-I-polarized T cells mediate more potent graft-versus-tumor (GVT) 
      effects. This phase I translational study evaluated adoptive transfer of ex vivo 
      costimulated type-I/type-II (T1/T2) donor T cells with T-cell-depleted (TCD) 
      allogeneic stem cell transplantation (AlloSCT) for MBC. EXPERIMENTAL DESIGN: 
      Patients had received anthracycline, taxane, and antibody therapies, and been 
      treated for metastatic disease and a human leukocyte antigen 
      (HLA)-identical-sibling donor. Donor lymphocytes were costimulated ex vivo with 
      anti-CD3/anti-CD28 antibody-coated magnetic beads in interleukin 
      (IL)-2/IL-4-supplemented media. Patients received reduced intensity conditioning, 
      donor stem cells and T1/T2 cells, and monitoring for toxicity, engraftment, GVHD, 
      and tumor response; results were compared with historical controls, identically 
      treated except for T1/T2 product infusions. RESULTS: Mixed type-I/type-II CD4(+) 
      T cells predominated in T1/T2 products. Nine patients received T1/T2 cells at 
      dose level 1 (5 x 10(6) cells/kg). T-cell donor chimerism reached 100% by a 
      median of 28 days. Seven (78%) developed acute GVHD. At day +28, five patients 
      had partial responses (56%) and none had MBC progression; thereafter, two 
      patients had continued responses. Donor T-cell engraftment and tumor responses 
      appeared faster than in historical controls, but GVHD rates were similar and 
      responders progressed early, often following treatment of acute GVHD. CONCLUSION: 
      Allogeneic T1/T2 cells were safely infused with TCD-AlloSCT, appeared to promote 
      donor engraftment, and may have contributed to transient early tumor responses.
CI  - (c)2011 AACR
FAU - Hardy, Nancy M
AU  - Hardy NM
AD  - Experimental Transplantation and Immunology Branch, Center for Cancer Research, 
      National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. 
      hardyn@mail.nih.gov
FAU - Mossoba, Miriam E
AU  - Mossoba ME
FAU - Steinberg, Seth M
AU  - Steinberg SM
FAU - Fellowes, Vicki
AU  - Fellowes V
FAU - Yan, Xiao-Yi
AU  - Yan XY
FAU - Hakim, Frances T
AU  - Hakim FT
FAU - Babb, Rebecca R
AU  - Babb RR
FAU - Avila, Daniele
AU  - Avila D
FAU - Gea-Banacloche, Juan
AU  - Gea-Banacloche J
FAU - Sportes, Claude
AU  - Sportes C
FAU - Levine, Bruce L
AU  - Levine BL
FAU - June, Carl H
AU  - June CH
FAU - Khuu, Hahn M
AU  - Khuu HM
FAU - Carpenter, Ashley E
AU  - Carpenter AE
FAU - Krumlauf, Michael C
AU  - Krumlauf MC
FAU - Dwyer, Andrew J
AU  - Dwyer AJ
FAU - Gress, Ronald E
AU  - Gress RE
FAU - Fowler, Daniel H
AU  - Fowler DH
FAU - Bishop, Michael R
AU  - Bishop MR
LA  - eng
SI  - ClinicalTrials.gov/NCT00082953
GR  - Y99 CA999999/CA/NCI NIH HHS/United States
GR  - Z99 CA999999/ImNIH/Intramural NIH HHS/United States
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
DEP - 20110926
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
SB  - IM
MH  - Adult
MH  - Breast Neoplasms/immunology/pathology/surgery/*therapy
MH  - Female
MH  - Graft vs Tumor Effect/immunology
MH  - Humans
MH  - Immunotherapy, Adoptive/*methods
MH  - Middle Aged
MH  - Neoplasm Metastasis
MH  - Stem Cell Transplantation
MH  - T-Lymphocytes/*immunology
PMC - PMC3206984
MID - NIHMS326939
COIS- Conflict of Interest Statement: CH June has royalties from US Government owned 
      patents and patent applications in the field of adoptive immunotherapy. This 
      arrangement is under compliance with the policies of the University of 
      Pennsylvania.
EDAT- 2011/09/29 06:00
MHDA- 2012/01/21 06:00
PMCR- 2012/11/01
CRDT- 2011/09/28 06:00
PHST- 2011/09/28 06:00 [entrez]
PHST- 2011/09/29 06:00 [pubmed]
PHST- 2012/01/21 06:00 [medline]
PHST- 2012/11/01 00:00 [pmc-release]
AID - 1078-0432.CCR-11-1579 [pii]
AID - 10.1158/1078-0432.CCR-11-1579 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2011 Nov 1;17(21):6878-87. doi: 10.1158/1078-0432.CCR-11-1579. 
      Epub 2011 Sep 26.