Parameters involved in the enhancement of monoclonal antibody targeting in vivo with recombinant interferon.
The effects of recombinant human leukocyte (clone A) interferon (rHu-IFN-alpha A) were investigated on the expression of monoclonal antibody (MAb)-defined tumor antigens expressed on human mammary and colon carcinomas. The rHu-IFN-alpha A treatment substantially increased the localization of radiolabeled MAb B6.2-F(ab')2 to the transplantable Clouser human mammary carcinoma, as well as to the moderately differentiated human colon xenograft WiDr, when grown as s.c. tumors in athymic mice. In contrast, human tumor cell lines (i.e., LS174T, A375, etc.) that were unresponsive to the antigen-augmenting ability of rHu-IFN-alpha A in vitro were also unresponsive in vivo, indicating a possible method of screening carcinoma cell populations for subsequent rHu-IFN-alpha A adjuvant therapy prior to MAb administration. The method of delivery of rHu-IFN-alpha A was also studied. The i.m. route resulted in a 3-4 h plasma half-life for rHu-IFN-alpha A. The administration of rHu-IFN-alpha A via an osmotic pump resulted in a stable circulating plasma titer of 400-800 antiviral units/ml for 7 days. Utilizing delivery of rHu-IFN-alpha A by the constant infusion route, it was found that the increase in localization of 125I-B6.2-F(ab')2 was dependent on (1) the length of time of treatment and (2) the circulating plasma rHu-IFN-alpha A levels. These results thus provide information useful for subsequent studies to determine the potential efficacy of adjuvant rHu-IFN-alpha A treatment for MAb-targeted tumor diagnosis and treatment.
Guadagni
F
F
Laboratory of Tumor Immunology and Biology, National Cancer Institute, Bethesda, Maryland 20892.
Schlom
J
J
Pothen
S
S
Pestka
S
S
Greiner
J W
JW
D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000097:blood; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D001666:Binding Sites, Antibody; D001943:Breast Neoplasms / Q000276:immunology; D002277:Carcinoma / Q000276:immunology*; D002460:Cell Line; D003110:Colonic Neoplasms / Q000276:immunology; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007370:Interferon Type I / Q000008:administration & dosage* / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011994:Recombinant Proteins / Q000008:administration & dosage* / Q000097:blood
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D007370:Interferon Type I; D011994:Recombinant Proteins