• P Hu, J L Hornick, M S Glasky, A Yun, M N Milkie, L A Khawli, P M Anderson, and A L Epstein.
• Department of Pathology, University of Southern California School of Medicine, Los Angeles 90033, USA.
• Cancer Res. 1996 Nov 1; 56 (21): 4998-5004.

AbstractA murine antihuman B-cell monoclonal antibody, Lym-1, has shown considerable promise for the treatment of human malignant lymphomas. To enhance its clinical potential, a genetically engineered fusion protein consisting of a chimeric Lym-1 (chLym-1) and interleukin 2 (IL-2) was tested for mediating cytotoxicity, increasing vasopermeability, and enhancing antibody uptake in human malignant lymphomas. The chLym-1/IL-2 fusion protein, which was expressed initially in a baculovirus system and more recently in the glutamine synthetase gene amplification system, was shown to be processed and assembled into a normal immunoglobulin monomer with two IL-2 molecules per antibody. It was found to be equivalent to the chLym-1 antibody in antigen-binding specificity and relative affinity. In addition, it maintains IL-2 cytokine activity as demonstrated by support of T-cell proliferation. Moreover, in antibody-dependent cellular cytotoxicity assays against Raji target cells, chLym-1/IL-2 had approximately 2-fold and 4-fold higher cytotoxicity than chLym-1 and murine Lym-1, respectively. Used as a pretreatment, chLym-1/IL-2 enhances the uptake of chLym-1 at the tumor site by altering the permeability of tumor vessels producing tumor:normal organ ratios of 420:1 for blood and 1708:1 for muscle at 3 days. The in vitro and in vivo activities of chLym-1/IL-2, therefore, suggest that this genetically engineered antibody fusion protein may represent a new immunotherapeutic reagent for the treatment of human malignant lymphomas.

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