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¹ Departments of Biological Chemistry and ² Immunology, Weizmann Institute of Science; and ³ Department of Hematology, Kaplan Medical Center, Rehovot, Israel

Requests for reprints: David Mirelman, Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel. Phone: 972-8-9344511; Fax: 972-8-9468256. E-mail: david.mirelman{at}weizmann.ac.il

Allicin, a highly active component from freshly crushed garlic, is produced upon the reaction of the small molecular weight molecule alliin, with the enzyme alliinase (EC 4.4.1.4). Because allicin was shown to be toxic to various mammalian cells in vitro, we devised a novel approach for the therapy of B-cell malignancies based on site-directed generation of allicin. Alliinase was conjugated to the monoclonal antibody rituximab, which recognizes the CD20 antigen, and the resulting conjugate was targeted to CD20⁺ B chronic lymphocytic leukemia (B-CLL) and other B-cell lymphomas. Upon addition of alliin, allicin was formed in situ, killing the CD20⁺ tumor B cells via apoptosis. Following a 72-hour treatment, an 85% and 96% reduction was observed in the number of viable B-CLL and EBV-transformed B cells, respectively. Using the human/mouse radiation chimera for the evaluation of allicin targeting in a preclinical animal model, we showed a significant reduction in the number of recovered B-CLL, mantle cell lymphoma, or EBV-transformed B cells. We conclude that our system offers a new powerful and less toxic therapy for B-CLL and other B-cell malignancies. Furthermore, combining alliinase with the appropriate monoclonal antibody may extend the application of this approach to other conditions in which the elimination of a specific cell population is desired.

Key Words: B-Cell Malignancies • Alliin • Rituximab-Alliinase Conjugate • Allicin

Grant support: Grants from Morross Institute for Cancer Research at the Weizmann Institute of Science and from N. Minzly, England.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 8/24/04; revised 11/23/04; accepted 12/ 1/04.