title: Phase I trial of adoptive cell transfer with mixed-profile type-I/type-II allogeneic T cells for metastatic breast cancer.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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 × 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.
  
  
  CONCLUSIONS
  Allogeneic T1/T2 cells were safely infused with TCD-AlloSCT, appeared to promote donor engraftment, and may have contributed to transient early tumor responses.
authors.affiliation: Experimental Transplantation and Immunology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. hardyn@mail.nih.gov
authors.forename: Nancy M
authors.initials: NM
authors.lastname: Hardy
authors.forename: Miriam E
authors.initials: ME
authors.lastname: Mossoba
authors.forename: Seth M
authors.initials: SM
authors.lastname: Steinberg
authors.forename: Vicki
authors.initials: V
authors.lastname: Fellowes
authors.forename: Xiao-Yi
authors.initials: XY
authors.lastname: Yan
authors.forename: Frances T
authors.initials: FT
authors.lastname: Hakim
authors.forename: Rebecca R
authors.initials: RR
authors.lastname: Babb
authors.forename: Daniele
authors.initials: D
authors.lastname: Avila
authors.forename: Juan
authors.initials: J
authors.lastname: Gea-Banacloche
authors.forename: Claude
authors.initials: C
authors.lastname: Sportès
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Levine
authors.forename: Carl H
authors.initials: CH
authors.lastname: June
authors.forename: Hahn M
authors.initials: HM
authors.lastname: Khuu
authors.forename: Ashley E
authors.initials: AE
authors.lastname: Carpenter
authors.forename: Michael C
authors.initials: MC
authors.lastname: Krumlauf
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Dwyer
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Gress
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Fowler
authors.forename: Michael R
authors.initials: MR
authors.lastname: Bishop
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000276:immunology / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D005260:Female; D020350:Graft vs Tumor Effect / Q000276:immunology; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D033581:Stem Cell Transplantation; D013601:T-Lymphocytes / Q000276:immunology*