Selective cytotoxicity of murine monoclonal antibody LAM2 against human small-cell carcinoma in the presence of human complement: possible use for in vitro elimination of tumor cells from bone marrow.
LAM2 is a murine IgM monoclonal antibody (MAb) which binds strongly to the cell membrane of human lung small-cell carcinoma (SCC) and squamous-cell carcinoma but not to normal bone-marrow cells. The cytotoxicity of this antibody in the presence of human complement was investigated in vitro by chromium release and clonogenic assays. The optimal treatment conditions included incubation with antibody for 30 min at 37 degrees C followed by 3 additions of human complement 30 min apart. Cell lysis ranged from 94 to 98% in 4 SCC cell lines at antibody dilutions of 1:100: a lower level of lysis (60%) occurred in a lung squamous-cell carcinoma cell line. The cytotoxic effect was strictly complement-dependent. No cytotoxic effect was seen with other human cell lines including lung adenocarcinoma, lung large-cell carcinoma, myeloid leukemia, and lymphoblastic leukemia. No lysis was seen with nucleated marrow cells from healthy volunteers. Normal marrow cells in excess did not inhibit SCC cell lysis. Incubation with antibody and complement resulted in a 100-fold reduction of colony formation of SCC cells, but did not reduce the number of colonies of marrow-cell precursors, including CFU-GEMM, BFU-E, and CFU-C. The selective cytotoxicity of LAM2 antibody to SCC, but not to normal bone-marrow cells, suggests that this antibody may be useful for the in vitro elimination of SCC cells from the bone marrow.
Stahel
R A
RA
Mabry
M
M
Sabbath
K
K
Speak
J A
JA
Bernal
S D
SD
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000627:therapeutic use; D000920:Antibody-Dependent Cell Cytotoxicity; D001853:Bone Marrow / Q000276:immunology / Q000473:pathology*; D016026:Bone Marrow Transplantation; D018288:Carcinoma, Small Cell / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D002460:Cell Line; D003114:Colony-Forming Units Assay; D003165:Complement System Proteins / Q000276:immunology; D003470:Culture Media; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000473:pathology; D006801:Humans; D008175:Lung Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D051379:Mice; D014411:Neoplastic Stem Cells / Q000276:immunology* / Q000473:pathology; D013234:Stem Cells / Q000276:immunology*; D014182:Transplantation, Autologous; D014410:Tumor Stem Cell Assay
D000911:Antibodies, Monoclonal; D003470:Culture Media; D003165:Complement System Proteins