An IgG3-IL-2 fusion protein recognizing a murine B cell lymphoma exhibits effective tumor imaging and antitumor activity.
Antibody (Ab)-based tumor therapeutics use the tumor-binding specificity of the Ab to target Fc functions or associated molecules to the site of the tumor. We have used an Ab-interleukin-2 (IL-2) fusion protein to deliver IL-2 to a murine B cell lymphoma (38C13). This anti-Id IgG3-CH3-IL-2, which recognizes the idiotype present on the surface of the lymphoma has a half-life in mice approximately 17-fold longer than the half-life reported for IL-2. Gamma camera studies showed that anti-Id IgG3-CH3-IL-2 localizes at the site of a subcutaneous tumor in mice. The anti-Id IgG3-CH3-IL-2 also shows enhanced antitumor activity compared with the combination of Ab and IL-2 administered together. However, the mechanism of antitumor activity appears to depend on the dose and the treatment schedule used. A single dose of fusion protein prevented tumor in only 50% of the animals, although all the survivors showed some evidence of immunologic memory. Although multiple doses are more effective in preventing tumor growth (87% survivors), they are ineffective in generating protective immunologic memory. Our results suggest that Ab-IL-2 fusion proteins will be useful in the diagnosis and treatment of human B cell lymphomas and other related malignancies.
Penichet
M L
ML
Department of Microbiology and Molecular Genetics, Molecular Biology Institute, University of California, Los Angeles 90095-1489, USA.
Harvill
E T
ET
Morrison
S L
SL
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000627:therapeutic use*; D000937:Antigen-Antibody Reactions; D000951:Antigens, Neoplasm / Q000276:immunology; D000970:Antineoplastic Agents / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D015902:Gamma Cameras; D006207:Half-Life; D007074:Immunoglobulin G / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000627:therapeutic use*; D016393:Lymphoma, B-Cell / Q000000981:diagnostic imaging / Q000628:therapy*; D051379:Mice; D008809:Mice, Inbred C3H; D008819:Mice, Nude; D011877:Radionuclide Imaging; D011993:Recombinant Fusion Proteins / Q000276:immunology*
D000888:Antibodies, Anti-Idiotypic; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D007074:Immunoglobulin G; D007376:Interleukin-2; D011993:Recombinant Fusion Proteins