Suppression of human melanoma tumor growth in SCID mice by a human high molecular weight-melanoma associated antigen (HMW-MAA) specific monoclonal antibody.
The lack of efficacy of available therapies for the treatment of malignant melanoma has emphasized the need to develop novel therapeutic strategies to prevent melanoma growth. We have tested whether the anti-HMW-MAA mAb 225.28S is able to inhibit human melanoma tumor growth in SCID mice because in vitro data suggested that this antigen plays a role in spreading, migration and invasion of melanoma cells. Tumors were established by subcutaneous injection of the human melanoma cell line 518A2 into SCID mice. When tumors reached a size of 5 mm, the mAb 225.28S was administered intravenously 4 times in 3 day intervals at 100 microg/injection. Within 14 days after the first administration of the mAb 225.28S, tumor growth was reduced by 52% as compared to control mice. Three hundred and seven genes of >20,000 genes contained on the GeneChip were changed in their expression level at least 2-fold after administration of the mAb 225.28S. The encoded proteins were mostly components or modifiers of the extracellular matrix, tumor suppressors, and melanogenesis associated proteins. Surprisingly, the administration of the control mAb that did not lead to a significant tumor growth inhibition in vivo resulted in the modulation of two-thirds of these genes. This is the first report of suppression of human melanoma tumor growth in SCID mice by the mAb 225.28S. Our results suggest that anti-HMW-MAA mAbs may represent useful reagents to apply passive immunotherapy to patients with malignant melanoma.
Hafner
Christine
C
Department of Dermatology, Division of General Dermatology, Medical University of Vienna, Vienna, Austria.
Breiteneder
Heimo
H
Ferrone
Soldano
S
Thallinger
Christiane
C
Wagner
Stefan
S
Schmidt
Wolfgang M
WM
Jasinska
Joanna
J
Kundi
Michael
M
Wolff
Klaus
K
Zielinski
Christoph C
CC
Scheiner
Otto
O
Wiedermann
Ursula
U
Pehamberger
Hubert
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology*; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D049109:Cell Proliferation; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D016147:Genes, Tumor Suppressor; D006801:Humans; D007116:Immunization, Passive; D007262:Infusions, Intravenous; D008545:Melanoma / Q000473:pathology*; D058950:Melanoma-Specific Antigens; D051379:Mice; D016513:Mice, SCID; D008970:Molecular Weight; D009363:Neoplasm Proteins / Q000276:immunology*; D020411:Oligonucleotide Array Sequence Analysis; D012878:Skin Neoplasms / Q000473:pathology*; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins