题名：Adoptive therapy of head and neck squamous cell carcinoma with antibody coated immune cells: a pilot clinical trial.
作者：Riechelmann H, Wiesneth M, Schauwecker P, Reinhardt P, Gronau S, Schmitt A, Schroen C, Atz J, Schmitt M. Related Articles, Links
来源：Cancer Immunol Immunother[IF=4.086]. 2007 Feb 2; [Epub ahead of print]
摘要： Herbert Riechelmann1 , Markus Wiesneth2, Peter Schauwecker2, Peter Reinhardt2, Silke Gronau1, Anita Schmitt1, Carsten Schroen1, Judith Atz4 and Michael Schmitt3
(1) Department of Otorhinolaryngology, University Ulm, Frauensteige12, 89075 Ulm, Germany
(2) Institute for Clinical Infusion Medicine and Immunogenetics, Ulm, Germany
(3) Third Department of Internal Medicine, University Ulm, Ulm, Germany
(4) Fresenius Biotech GmbH, Graefelfing, Germany
Received: 12 September 2006 Accepted: 29 December 2006 Published online: 2 February 2007
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.
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.
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 1 104, 1 105, 1 106 and 1 107 CD3+ cells/kgBW intravenously at bi-weekly intervals.
After opsonization, PBMNC released substantial amounts of interferon (IFN) and tumor necrosis factor (TNF) in vitro, which were removed before administration. Catumaxomab up-regulated CD25, CD69, and CD83 on PBMNC, and catumaxomab loaded PBMNC released IFN 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 1 106 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.
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. Keywords Immunotherapy - Adoptive - Head and neck neoplasms - Antibodies - Bispecific - Antigens - Neoplasm - Leukapheresis - Cytokines - Clinical trials