title: Adoptive therapy of head and neck squamous cell carcinoma with antibody coated immune cells: a pilot clinical trial.
abstract: BACKGROUND
  Catumaxomab is an antibody that binds with one arm epithelial cell adhesion molecule (EpCAM) positive tumors and with the other arm CD3+ T cells. Intravenous application of therapeutic antibodies may result in intravascular cytokine release.
  
  
  OBJECTIVE
  In this pilot trial we assessed whether cytokine release can be controlled by ex vivo cell opsonization and cytokine wash-out before administration of catumaxomab, preserving its anti-cancer activity. In addition, preliminary data on safety of and clinical response to catumaxomab coated autologous immune cells were acquired.
  
  
  METHODS
  Peripheral blood mononuclear cells (PBMNC) of four patients with recurrent head and neck carcinoma were collected by leukapheresis, incubated ex vivo with catumaxomab for 24 h and cleared from released cytokines. Each patient received an escalated number of antibody-coated PBMNC equivalent to 1 x 10(4), 1 x 10(5), 1 x 10(6) and 1 x 10(7) CD3(+) cells/kgBW intravenously at bi-weekly intervals.
  
  
  RESULTS
  After opsonization, PBMNC released substantial amounts of interferon gamma (IFNgamma) and tumor necrosis factor alpha (TNFalpha) in vitro, which were removed before administration. Catumaxomab up-regulated CD25, CD69, and CD83 on PBMNC, and catumaxomab loaded PBMNC released IFNgamma and granzyme B when coincubated with EpCAM(+) BHY cells, suggesting cell activation and target directed biological activity. During the study period, one patient died of aspiration pneumonia and one patient needed a tracheotomy. Treatment related adverse events (AE) occurred at the highest cell dose in two patients, whereas 1 x 10(6) loaded CD3(+) cells/kgBW were well tolerated by all patients. One patient showed stable disease for 6 months and one patient is in complete remission for 27 months.
  
  
  CONCLUSIONS
  Ex vivo opsonization of PBMNC with catumaxomab provided biologically active, tumor targeting cells. Extracorporeal PBMNC coating may be an option to control intravascular cytokine release induced by therapeutic antibodies.
authors.affiliation: Department of Otorhinolaryngology, University Ulm, Ulm, Germany. herbert.riechelmann@uniklinik-ulm.de
authors.forename: Herbert
authors.initials: H
authors.lastname: Riechelmann
authors.forename: Markus
authors.initials: M
authors.lastname: Wiesneth
authors.forename: Peter
authors.initials: P
authors.lastname: Schauwecker
authors.forename: Peter
authors.initials: P
authors.lastname: Reinhardt
authors.forename: Silke
authors.initials: S
authors.lastname: Gronau
authors.forename: Anita
authors.initials: A
authors.lastname: Schmitt
authors.forename: Carsten
authors.initials: C
authors.lastname: Schroen
authors.forename: Judith
authors.initials: J
authors.lastname: Atz
authors.forename: Michael
authors.initials: M
authors.lastname: Schmitt
mesh_terms: D018033:Antibodies, Bispecific / Q000378:metabolism / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000628:therapy*; D006258:Head and Neck Neoplasms / Q000276:immunology / Q000628:therapy*; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism; D016219:Immunotherapy, Adoptive; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D037181:Lectins, C-Type; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000637:transplantation; D008562:Membrane Glycoproteins / Q000378:metabolism; D010865:Pilot Projects; D015996:Survival Rate; D015854:Up-Regulation; D000097802:CD83 Antigen; D000099192:CD69 Antigens
chemical_list: D018033:Antibodies, Bispecific; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D007136:Immunoglobulins; D053645:Interleukin-2 Receptor alpha Subunit; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D000097802:CD83 Antigen; D000099192:CD69 Antigens; C522419:catumaxomab