Improved engraftment of human tumours in SCID mice pretreated with radiation and anti-asialo GM1.
The effects of sublethal radiation (3 Gy) and anti-asialo GM1 (anti-ASGM1) on engraftment of human tumour cell lines and fresh tumour were evaluated in the severe combined immunodeficient (SCID) mouse. Four tumour cell lines (colonic adenocarcinoma LS174T, malignant melanoma MEWO, lung adenocarcinoma H125, chronic myelogenous leukemia K562) and a fresh colon cancer metastasis were injected subcutaneously, intraperitoneally or intravenously into SCID mice. Tumour volume and metastatic spread of implanted tumours were evaluated 3-8 weeks following inoculation. Pretreatment with radiation and anti-ASGM1 resulted in more rapid and extensive uptake of subcutaneous and intraperitoneal tumours. Tail vein injection into pretreated animals also resulted in a greater number of lung metastases of H125, MEWO and K562 cell lines. This study demonstrates that sublethal radiation and the elimination of murine NK cell activity with anti-ASGM1 improves tumour take rates. These findings should prove useful for investigations of human cancer immunotherapy using SCID mice engrafted with human lymphocytes and human tumours.
Department of Surgery, Mount Sinai Hospital, University of Toronto, Ontario, Canada.
B
B
Shpitz
B J
BJ
Fernandes
J B
JB
Mullen
J C
JC
Roder
S
S
Gallinger
D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D002455:Cell Division / Q000502:physiology; D003601:Cytotoxicity Tests, Immunologic; D005260:Female; D005677:G(M1) Ganglioside / Q000276:immunology*; D006801:Humans; D007109:Immunity / Q000528:radiation effects; D008297:Male; D051379:Mice; D016513:Mice, SCID / Q000276:immunology*; D009368:Neoplasm Transplantation / Q000276:immunology* / Q000379:methods*; D009369:Neoplasms / Q000473:pathology; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured / Q000528:radiation effects
D000906:Antibodies; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside