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Adoptive therapy of head and neck squamous cell carcinoma with antibody coated immune cells: a pilot clinical trial.

AbstractBACKGROUND:
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.
AIM:
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.
CONCLUSION:
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.
AuthorsHerbert Riechelmann, Markus Wiesneth, Peter Schauwecker, Peter Reinhardt, Silke Gronau, Anita Schmitt, Carsten Schroen, Judith Atz, Michael Schmitt
JournalCancer immunology, immunotherapy : CII (Cancer Immunol Immunother) Vol. 56 Issue 9 Pg. 1397-406 (Sep 2007) ISSN: 0340-7004 [Print] Germany
PMID17273869 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antibodies, Bispecific
  • Antibodies, Monoclonal
  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD69 antigen
  • CD83 antigen
  • Immunoglobulins
  • Interleukin-2 Receptor alpha Subunit
  • Lectins, C-Type
  • Membrane Glycoproteins
  • catumaxomab
Topics
  • Antibodies, Bispecific (metabolism, therapeutic use)
  • Antibodies, Monoclonal (therapeutic use)
  • Antigens, CD (metabolism)
  • Antigens, Differentiation, T-Lymphocyte (metabolism)
  • Carcinoma, Squamous Cell (immunology, therapy)
  • Head and Neck Neoplasms (immunology, therapy)
  • Humans
  • Immunoglobulins (metabolism)
  • Immunotherapy, Adoptive
  • Interleukin-2 Receptor alpha Subunit (metabolism)
  • Lectins, C-Type
  • Leukocytes, Mononuclear (immunology, transplantation)
  • Membrane Glycoproteins (metabolism)
  • Pilot Projects
  • Survival Rate
  • Up-Regulation

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