Abstract | BACKGROUND: 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.
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Authors | Herbert Riechelmann, Markus Wiesneth, Peter Schauwecker, Peter Reinhardt, Silke Gronau, Anita Schmitt, Carsten Schroen, Judith Atz, Michael Schmitt |
Journal | Cancer immunology, immunotherapy : CII
(Cancer Immunol Immunother)
Vol. 56
Issue 9
Pg. 1397-406
(Sep 2007)
ISSN: 0340-7004 [Print] Germany |
PMID | 17273869
(Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
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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
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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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