title: Targeted T-cell Therapy in Stage IV Breast Cancer: A Phase I Clinical Trial.
abstract: OBJECTIVE
  This study reports a phase I immunotherapy trial in 23 women with metastatic breast cancer consisting of eight infusions of anti-CD3 × anti-HER2 bispecific antibody (HER2Bi) armed anti-CD3-activated T cells (ATC) in combination with low-dose IL-2 and granulocyte-macrophage colony-stimulating factor to determine safety, maximum tolerated dose (MTD), technical feasibility, T-cell trafficking, immune responses, time to progression, and overall survival (OS).
  
  
  METHODS
  ATC were expanded from leukapheresis product using IL2 and anti-CD3 monoclonal antibody and armed with HER2Bi. In 3+3 dose escalation design, groups of 3 patients received 5, 10, 20, or 40 × 10(9) armed ATC (aATC) per infusion.
  
  
  RESULTS
  There were no dose-limiting toxicities and the MTD was not defined. It was technically feasible to grow 160 × 10(9) ATC from a single leukapheresis. aATC persisted in the blood for weeks and trafficked to tumors. Infusions of aATC induced anti-breast cancer responses and increases in immunokines. At 14.5 weeks after enrollment, 13 of 22 (59.1%) evaluable patients had stable disease and 9 of 22 (40.9%) had progressive disease. The median OS was 36.2 months for all patients, 57.4 months for HER2 3+ patients, and 27.4 months for HER2 0-2+ patients.
  
  
  CONCLUSIONS
  Targeting HER2(+) and HER2(-) tumors with aATC infusions induced antitumor responses, increases in Th1 cytokines, and IL12 serum levels that suggest that aATC infusions vaccinated patients against their own tumors. These results provide a strong rationale for conducting phase II trials.
authors: Department of Oncology, Wayne State University and Karmanos Cancer Institute, Detroit, Michigan. Department of Medicine, Wayne State University and Karmanos Cancer Institute, Detroit, Michigan. Department of Immunology and Microbiology, Wayne State University and Karmanos Cancer Institute, Detroit, Michigan. luml@karmanos.org thakur@karmanos.org.
authors: Lawrence G
authors: LG
authors: Lum
authors: Department of Oncology, Wayne State University and Karmanos Cancer Institute, Detroit, Michigan. luml@karmanos.org thakur@karmanos.org.
authors: Archana
authors: A
authors: Thakur
authors: Department of Oncology, Wayne State University and Karmanos Cancer Institute, Detroit, Michigan. Department of Medicine, Wayne State University and Karmanos Cancer Institute, Detroit, Michigan.
authors: Zaid
authors: Z
authors: Al-Kadhimi
authors: South County Hospital, Wakefield, Rhode Island.
authors: Gerald A
authors: GA
authors: Colvin
authors: Division of Hematology and Oncology, Department of Medicine, Roger Williams Hospital, Providence, Rhode Island.
authors: Francis J
authors: FJ
authors: Cummings
authors: Women & Infants Hospital, Providence, Rhode Island.
authors: Robert D
authors: RD
authors: Legare
authors: Massachusetts General Hospital Cancer Center, Department of Medicine, Harvard Medical School, Boston, Massachusetts.
authors: Don S
authors: DS
authors: Dizon
authors: Department of Pathology, Roger Williams Medical Center, Providence, Rhode Island.
authors: Nicola
authors: N
authors: Kouttab
authors: Women & Infants Hospital, Providence, Rhode Island.
authors: Abby
authors: A
authors: Maizel
authors: Department of Nuclear Medicine, Roger Williams Medical Center, Providence, Rhode Island.
authors: William
authors: W
authors: Colaiace
authors: Department of Medicine, Wistar Institute, Philadelphia, Pennsylvania.
authors: Qin
authors: Q
authors: Liu
authors: Division of Hematology and Oncology, Department of Medicine, Roger Williams Hospital, Providence, Rhode Island.
authors: Ritesh
authors: R
authors: Rathore
mesh_terms: D000328:Adult; D000368:Aged; D018033:Antibodies, Bispecific / Q000008:administration & dosage; D001943:Breast Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D007167:Immunotherapy; D007376:Interleukin-2 / Q000008:administration & dosage; D053208:Kaplan-Meier Estimate; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation*
chemical_list: D018033:Antibodies, Bispecific; D007376:Interleukin-2; D016178:Granulocyte-Macrophage Colony-Stimulating Factor