Biological study of R24 mouse monoclonal antibody in patients undergoing thoracotomy for pulmonary metastases from soft tissue sarcoma.
The disialoganglioside GD3 is expressed on the surface of soft tissue sarcoma, malignant melanoma, and other malignant cells and is, therefore, a potential target for therapeutic monoclonal antibodies. Intravenously administered R24, a murine IgG3 monoclonal antibody to GD3, induces inflammation and tumor regression at sites of metastatic malignant melanoma. R24 5 mg/m2 was given intravenously every other day for six doses to 10 patients with pulmonary metastases from a primary soft tissue sarcoma of the extremity for whom thoracotomy was planned. Resected tissue was available from 7 patients. All metastases expressed GD3; however, expression was heterogeneous within tumors, and in no tumor were more than 80% of the cells GD3 positive. A mild to moderate infiltrate consisting of mononuclear cells with T-cell markers was identified around or within pulmonary metastases in 6 patients. Tolerable acute allergic reactions occurred in all patients, but 3 patients had severe chest tightness and bronchospasm that limited the planned therapy. The setting of thoracotomy for metastatic disease provides an ideal system for studies on the pharmacology and biological effects of monoclonal antibodies that target soft tissue sarcoma antigens.
Casper
E S
ES
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York.
Cordon-Cardo
C
C
Houghton
A N
AN
Steffens
T A
TA
McCormack
P
P
Magill
G B
GB
Hajdu
S I
SI
Brennan
M F
MF
D000328:Adult; D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D004155:Diphenhydramine / Q000627:therapeutic use; D004837:Epinephrine / Q000627:therapeutic use; D005260:Female; D005732:Gangliosides / Q000096:biosynthesis / Q000276:immunology*; D018219:Histiocytoma, Benign Fibrous / Q000473:pathology / Q000556:secondary / Q000601:surgery / Q000628:therapy; D006801:Humans; D006825:Hybridomas; D007262:Infusions, Intravenous; D007428:Intradermal Tests; D007866:Leg; D008080:Liposarcoma / Q000473:pathology / Q000556:secondary / Q000601:surgery / Q000628:therapy; D008175:Lung Neoplasms / Q000473:pathology / Q000556:secondary* / Q000601:surgery / Q000628:therapy; D008297:Male; D051379:Mice; D008875:Middle Aged; D012516:Osteosarcoma / Q000473:pathology / Q000556:secondary / Q000601:surgery / Q000628:therapy; D012509:Sarcoma / Q000473:pathology / Q000556:secondary / Q000601:surgery / Q000628:therapy*; D012983:Soft Tissue Neoplasms / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D013848:Thigh
D000911:Antibodies, Monoclonal; D005732:Gangliosides; C026226:ganglioside, GD3; D004155:Diphenhydramine; D004837:Epinephrine