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In Vivo Activity of Solid Phase Interleukin 2¹

Departments of Medicine [E. D. C.] and Pathology [D. R. K.], Ireland Cancer Center, University Hospitals of Cleveland, Case Western Reserve University Cancer Center, Cleveland, Ohio 44106

Interleukin 2 (IL-2) coupled to polystyrene beads to form a solid phase of the cytokine was able to increase the cytotoxic activity of rat spleen cells in vitro. A single injection of the IL-2 coupled beads into the peritoneal cavities of normal rats also resulted in the in vivo activation of cytotoxicity of peritoneal exudate cells, whereas a single i.p. injection of the same amount of soluble IL-2 was not effective. When IL-2 coupled beads were mixed with methylcholanthrene-induced Mc7 or Mc107 sarcoma cells and injected into normal syngeneic Wistar rats, the growth of the tumor was suppressed. This effect was localized to the site of the injection. The in vivo activities were achieved with modest amounts of IL-2, less than has been previously reported to be well tolerated in rodents. IL-2 coupled to a solid matrix may be useful for delivering increased concentrations of the lymphokine to tumor dominant regions while maintaining low systemic levels and thereby increasing the therapeutic index.

¹ Supported by the Ireland Cancer Center, a grant from the Bristol-Myers Co., Grants AA-07385 and CA-43703, and a fellowship from the Hartford Foundation.

² To whom requests for reprints should be addressed, at University Hospitals of Cleveland, 2074 Abington Road, Cleveland, OH 44106.

Received 2/16/90. Accepted 11/19/90.