title: A phase I trial of immunotherapy with lapuleucel-T (APC8024) in patients with refractory metastatic tumors that express HER-2/neu.
abstract: OBJECTIVE
  This study aimed to evaluate the safety of, immune response induced by, and efficacy of treatment with lapuleucel-T (APC8024) in patients with HER-2/neu-expressing tumors. Lapuleucel-T is an investigational active immunotherapy product consisting of autologous peripheral blood mononuclear cells, including antigen presenting cells, which are cultured ex vivo with BA7072, a recombinant fusion antigen consisting of portions of the intracellular and extracellular regions of HER-2/neu linked to granulocyte-macrophage colony-stimulating factor.
  
  
  METHODS
  Patients with metastatic breast, ovarian, or colorectal cancer whose tumors expressed HER-2 were eligible. Patients underwent leukapheresis in week 0 and received lapuleucel-T infusions in weeks 0, 2, and 4. Patients who achieved a partial response or had stable disease through week 48 were eligible for re-treatment using the same protocol and dose as their initial treatment.
  
  
  RESULTS
  Eighteen patients were enrolled and treated. Patients showed an immune response to the immunizing antigen (BA7072) at week 8 compared with week 0 as measured by T lymphocyte proliferation and IFN-gamma enzyme-linked immunospot assay. Therapy was well tolerated. The majority (94.7%) of adverse events associated with treatment were grade 1 or 2. Two patients experienced stable disease lasting > 48 weeks.
  
  
  CONCLUSIONS
  Autologous active cellular immunotherapy with lapuleucel-T stimulated an immune response specific to the immunizing antigen and seemed to be well tolerated. Further clinical studies to assess the clinical benefit for patients with HER/2-neu-expressing breast, ovarian, and colorectal cancer are warranted.
authors.affiliation: Mayo Clinic, Rochester, Minnesota 55905, USA. peethambaram.prema@mayo.edu
authors.forename: Prema P
authors.initials: PP
authors.lastname: Peethambaram
authors.forename: Michelle E
authors.initials: ME
authors.lastname: Melisko
authors.forename: Kristine J
authors.initials: KJ
authors.lastname: Rinn
authors.forename: Steven R
authors.initials: SR
authors.lastname: Alberts
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Provost
authors.forename: Lori A
authors.initials: LA
authors.lastname: Jones
authors.forename: Robert B
authors.initials: RB
authors.lastname: Sims
authors.forename: Lisa R C
authors.initials: LR
authors.lastname: Lin
authors.forename: Mark W
authors.initials: MW
authors.lastname: Frohlich
authors.forename: John W
authors.initials: JW
authors.lastname: Park
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000276:immunology / Q000556:secondary / Q000628:therapy*; D019496:Cancer Vaccines / Q000276:immunology*; D015179:Colorectal Neoplasms / Q000276:immunology / Q000556:secondary / Q000628:therapy*; D005260:Female; D006801:Humans; D007167:Immunotherapy; D008297:Male; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000276:immunology / Q000556:secondary / Q000628:therapy*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis* / Q000097:blood / Q000276:immunology
chemical_list: D019496:Cancer Vaccines; D018719:Erb-b2 Receptor Tyrosine Kinases; C522647:Lapuleucel-T; C508053:ERBB2 protein, human