Effect of tumor size on the enhancement by gamma interferon of the localization of radiolabeled F(ab')2 fragments of anti-intercellular adhesion molecule-1 monoclonal antibodies in human colon carcinoma cells grafted in nude mice.
Because tumor size has been shown to influence the specific accumulation of radiolabeled anti-tumor-associated antigen monoclonal antibodies (mAb), the present study has investigated the effect of the tumor size on the enhancement by gamma interferon (IFN-gamma) of the accumulation of radiolabeled mAb in malignant lesions. Intercellular adhesion molecule-1 (ICAM-1) has been used as a marker because of its high susceptibility to modulation by IFN-gamma. F(ab')2 fragments of anti-ICAM-1 mAb CL207.14 have been selected to visualize malignant lesions, because they had been shown to be more sensitive probes for our experiments than whole IgG. Administration of IFN-gamma to human colon carcinoma-bearing nude mice increased the expression of ICAM-1 in the xenografts and the specific accumulation of 125I-F(ab')2 fragments of anti-ICAM-1 mAb CL207.14. The latter effect is influenced by the size of the lesions, because it was observed only in tumors with an approximate diameter of 8 mm and an approximate weight of 250 mg. If these results obtained in an animal model system are applicable to patients with malignant diseases, the present investigation suggests that administration of IFN-gamma enhances the sensitivity of immunoscintigraphy and the efficacy of immunotherapy with radiolabeled mAb which recognize tumor-associated antigens that are susceptible to modulation by IFN-gamma. However, the effect of IFN-gamma is not a general phenomenon but is influenced by the size of the malignant lesions.
Institute for Biomedical Research, Osaka, Japan.
M
M
Matsui
S
S
Yoshimura
T
T
Nakanishi
S
S
Ferrone
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000276:immunology* / Q000378:metabolism; D003110:Colonic Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma / Q000494:pharmacology*; D007457:Iodine Radioisotopes; D051379:Mice; D008819:Mice, Nude; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D007140:Immunoglobulin Fab Fragments; D007457:Iodine Radioisotopes; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma