Inhibition of the growth of human melanoma metastases in nude mice by melanoma-specific murine monoclonal antibody.
The administration of anti-melanoma murine monoclonal antibody (MAB) 16.C8 (IgG2a) to nude mice bearing established human melanoma lung or liver metastases resulted in a significant inhibition of tumour growth. A total dose of 2 mg of affinity purified 16.C8 caused complete inhibition of tumour growth in 89 and 100% of animals in the liver and lung model, respectively. In contrast, a significant tumour growth was found in most control animals which received an irrelevant IgG2a MAB or 2% human serum albumin in Hanks Balanced Salt Solution (HBSS). The MAB was most effective when treatment was started on day 1 or 4 following tumour inoculation. When the 16.C8 MAB treatment was delayed 7 or 14 days, 33 and 67% of 16.C8 treated animals, respectively, developed tumours. The MAB-mediated anti-tumour activity appeared to be dose dependent, and the effect of a suboptimal dose was potentiated by the concomitant administration of recombinant interleukin 2 (rIL-2). Recombinant IL-2 alone in a similar dose did not elicit comparable anti-tumour activity. Moreover, the MAB 16.C8 inhibited tumour growth in irradiated animals which may suggest the involvement of host-radioresistant cellular elements in the 16.C8 antibody-mediated anti-tumour activities in nude mice. These results suggest that MAB 16.C8 alone or combined with rIL-2 may prove useful in the immunotherapy of metastatic melanoma.
Abdel-Wahab
Z A
ZA
Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710.
Darrow
T L
TL
Vervaert
C E
CE
Giannopoulou
A A
AA
Li
W
W
Seigler
H F
HF
D000818:Animals; D000911:Antibodies, Monoclonal / Q000302:isolation & purification / Q000627:therapeutic use*; D000912:Antibodies, Neoplasm / Q000302:isolation & purification / Q000627:therapeutic use*; D000918:Antibody Specificity; D003131:Combined Modality Therapy; D004306:Dose-Response Relationship, Immunologic; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007376:Interleukin-2 / Q000627:therapeutic use; D008113:Liver Neoplasms / Q000276:immunology / Q000556:secondary* / Q000628:therapy*; D008175:Lung Neoplasms / Q000276:immunology / Q000556:secondary* / Q000628:therapy*; D008546:Melanoma, Experimental / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011994:Recombinant Proteins / Q000627:therapeutic use; D012878:Skin Neoplasms / Q000276:immunology / Q000628:therapy*; D014407:Tumor Cells, Cultured; D014916:Whole-Body Irradiation
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D007376:Interleukin-2; D011994:Recombinant Proteins