New monoclonal antibodies specific for human sarcomas

Abstract

Monoclonal antibodies (MAbs) against sarcoma-associated cell membrane antigens were prepared by immunizing BALB/c mice with tumor cells from a human osteosarcoma, TPX, grown as a xenograft in athymic BALB/c nude mice. Spleen cells from immunized mice were hybridized with X-63 Ag. 8.653 mouse myeloma cells which yielded 260 growing hybridomas. Seven of these produced antibodies that bound to TPX cells and to cells from another osteosarcoma, but not to autologous skin fibroblasts. MAbs from 2 (TP-1 and TP-3) of these 7 clones did not cross-react with non-sarcomatous tumor cells or peripheral blood lymphocytes. Immunohistochemical studies on frozen tissue sections showed that the TP-1 (IgG-2a) and TP-3 (IgG-2b) antibodies had characteristic and identical specificity profiles. Binding of TP-1 (TP-3) was demonstrated to 15/15 (15/15) osteosarcomas, 3/3 (2/2) synovial sarcomas, 7/9 (6/8) malignant fibrous histiocytomas, 2/2 (1/1) malignant hemangiopericytomas, 1/2 (1/2) chondrosarcomas and 3/6 (1/3) unclassified sarcomas. The antibodies did not bind to any of 16 sarcomas belonging to other histological subtypes, including liposarcomas and leio- and rhabdomyosarcomas. Moreover, they failed to bind to sections of 66 different non-sarcomatous malignancies, or to any of a range of normal adult and fetal tissues, although some weak staining of proximal kidney tubules was seen. The restricted specificity of these antibodies to some major subtypes of human sarcomas makes them promising tools for identification and subclassification of sarcomas.

Hematogenous Micrometastases in Osteosarcoma Patients

“…9.2.27 has been shown to bind also some subgroups of sarcoma, including osteosarcoma (39). Both mAbs have previously been shown nonreactive with mononuclear cells in peripheral blood and bone marrow from normal donors (34,39) and react poorly with fibroblastically differentiated osteosarcoma. 4 In addition, the MRK-16 mAb (Alexis Corp., Kamiya Biomedical Co., Seattle, WA) binding the multidrug resistance-associated p-glycoprotein 170 (MDR1), and the anti-melanoma mAb EP-1 (kindly provided by Dr. P.G.…”

Human heterophilic antibodies display specificity for murine IgG subclasses

“…Mabs TP-1 (IgG2a-n) and TP-3 (IgG2b-n) against sarcoma-associated cell membrane antigens [15] were kind gifts from ayvind Bruland and Steinar Funderud, The Norwegian Radium Hospital, while Mab FN4-16 (IgG3-n) against a B-cell surface antigen [16] was a gift from Steinar Funderud. Purified rat anti-CEA Mab GFR44 [17] was a gift from Brahms AG.…”

Intratumour injection of immunoglobulins labelled with the α-particle emitter 211At: analyses of tumour retention, microdistribution and growth delay

“…The MAb TP-3 of subclass IgG2b (Bruland et al, 1986), which recognizes an 80-kDa antigen commonly expressed in human osteosarcomas (Bruland et al, 1988), was used as antigen-specific antibody, while polyclonal human IgGi (Paus and Nustad, 1989) was used as a non-specific antibody.…”