This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hombach, A. Articles by Abken, H. Search for Related Content PubMed PubMed Citation Articles by Hombach, A. Articles by Abken, H.

An Anti-CD30 Chimeric Receptor That Mediates CD3--independent T-Cell Activation against Hodgkin's Lymphoma Cells in the Presence of Soluble CD30¹

Klinik 1 für Innere Medizin, Labor Tumorgenetik, Universität zu Köln, D-50924 Köln [A. H., C. H., R. S., T. T., V. D., H. A.], and Evangelisches Krankenhaus Köln-Kalk, D-51103 Köln [C. P.], Germany

Hodgkin's lymphoma patients fail to establish an efficient cellular response against CD30⁺ Hodgkin/Reed-Sternberg cells. An impaired T-cell receptor/CD3--mediated activation of T cells is thought to be involved in this situation. We here present a chimeric anti-CD30 receptor that mediates MHC and T-cell receptor/CD3--independent T-cell activation against CD30⁺ lymphoma cells even in the presence of soluble CD30. The receptor consists of the binding domain of the monoclonal antibody HRS3 and the signaling unit of the FcRI-receptor -chain. After expression in MD45 T cells, receptor cross-linking with immobilized anti-idiotypic monoclonal antibody and CD30⁺ cells, respectively, results in increased interleukin 2 secretion and specific cytolysis of CD30⁺ Hodgkin's lymphoma cells. Soluble CD30 in concentrations up to 6000 units/ml did not interfere with cellular activation induced by membrane-bound antigen. This demonstrates the feasibility of the chimeric anti-CD30-scFv- receptor in CD30⁺ lymphoma cell targeting, even in the presence of as high concentrations of soluble CD30 as are found in patients during progression of the disease.

¹ This study was supported by grants from the Deutsche Forschungsgemeinschaft through SFB502.

² To whom requests for reprints should be addressed, at Klinik I für Innere Medizin, Labor für Tumorgenetik, Universität zu Köln, Josef-Stelzmann-Strasse 9, D-50924 Köln, Germany. Phone: 49-221-478-4130; Fax: 49-221-478-6383; E-mail: hinrich.abken@medizin.uni-koeln.de.

Received 11/ 7/97. Accepted 1/26/98.

This article has been cited by other articles:

				A. Di Stasi, B. De Angelis, C. M. Rooney, L. Zhang, A. Mahendravada, A. E. Foster, H. E. Heslop, M. K. Brenner, G. Dotti, and B. Savoldo T lymphocytes coexpressing CCR4 and a chimeric antigen receptor targeting CD30 have improved homing and antitumor activity in a Hodgkin tumor model Blood, June 18, 2009; 113(25): 6392 - 6402. [Abstract] [Full Text] [PDF]

				K. Dobrenkov, M. Olszewska, Y. Likar, L. Shenker, G. Gunset, S. Cai, N. Pillarsetty, H. Hricak, M. Sadelain, and V. Ponomarev Monitoring the Efficacy of Adoptively Transferred Prostate Cancer-Targeted Human T Lymphocytes with PET and Bioluminescence Imaging J. Nucl. Med., July 1, 2008; 49(7): 1162 - 1170. [Abstract] [Full Text] [PDF]

				B. Savoldo, C. M. Rooney, A. Di Stasi, H. Abken, A. Hombach, A. E. Foster, L. Zhang, H. E. Heslop, M. K. Brenner, and G. Dotti Epstein Barr virus specific cytotoxic T lymphocytes expressing the anti-CD30{zeta} artificial chimeric T-cell receptor for immunotherapy of Hodgkin disease Blood, October 1, 2007; 110(7): 2620 - 2630. [Abstract] [Full Text] [PDF]

				R. A. Willemsen, C. Ronteltap, P. Chames, R. Debets, and R. L. H. Bolhuis T Cell Retargeting with MHC Class I-Restricted Antibodies: The CD28 Costimulatory Domain Enhances Antigen-Specific Cytotoxicity and Cytokine Production J. Immunol., June 15, 2005; 174(12): 7853 - 7858. [Abstract] [Full Text] [PDF]

				B. Savoldo, C. M. Rooney, H. E. Heslop, H. Abken, A. Hombach, L. Zhang, M. Pule, G. Dotti, and M. K. Brenner Epstein Barr Virus (EBV)-Specific Cytotoxic T Lymphocytes (CTL) Expressing an Anti-CD30 Chimeric T Cell Receptor (CTCR) for the Treatment of Hodgkin's Disease (HD). Blood (ASH Annual Meeting Abstracts), November 16, 2004; 104(11): 745 - 745. [Abstract]

				S. Reinartz, A. Hombach, S. Kohler, H. Schlebusch, D. Wallwiener, H. Abken, and U. Wagner Interleukin-6 Fused to an Anti-idiotype Antibody in a Vaccine Increases the Specific Humoral Immune Response against CA125+ (MUC-16) Ovarian Cancer Cancer Res., June 15, 2003; 63(12): 3234 - 3240. [Abstract] [Full Text] [PDF]

				A. Hombach, A. Wieczarkowiecz, T. Marquardt, C. Heuser, L. Usai, C. Pohl, B. Seliger, and H. Abken Tumor-Specific T Cell Activation by Recombinant Immunoreceptors: CD3{zeta} Signaling and CD28 Costimulation Are Simultaneously Required for Efficient IL-2 Secretion and Can Be Integrated Into One Combined CD28/CD3{zeta} Signaling Receptor Molecule J. Immunol., December 1, 2001; 167(11): 6123 - 6131. [Abstract] [Full Text] [PDF]

				A. Hombach, D. Sent, C. Schneider, C. Heuser, D. Koch, C. Pohl, B. Seliger, and H. Abken T-Cell Activation by Recombinant Receptors: CD28 Costimulation Is Required for Interleukin 2 Secretion and Receptor-mediated T-Cell Proliferation but Does Not Affect Receptor-mediated Target Cell Lysis Cancer Res., March 1, 2001; 61(5): 1976 - 1982. [Abstract] [Full Text]

				M. Brenner, C. Rossig, U. Sili, J. W. Young, and E. Goulmy Transfusion Medicine: New Clinical Applications of Cellular Immunotherapy Hematology, January 1, 2000; 2000(1): 356 - 375. [Abstract] [Full Text] [PDF]