Quantitative comparison between the transplantability of human and murine tumors into the subcutaneous tissue of NCr/Sed-nu/nu nude and severe combined immunodeficient mice.
In previous reports, nude mice have demonstrated residual immunoreactivity against xenografts. Severe combined immunodeficient (SCID) mice lack functional T- and B-cells. These animals are expected to be better hosts in which to perform preclinical studies on human tumors. The purpose of this study is to quantitate the advantage of SCID mice over nude mice in terms of transplantability of human and murine tumors and the importance of residual immunity in SCID mice. The transplantation assays are described by an assay based on the number of tumor cells required to transplant tumor into 50% of recipients (TD50). Seven human tumors of different histology and four murine tumor cell lines were used. Serial 2-10-fold dilutions of cells were injected (0.1 ml) into the flanks of normal and whole-body irradiated WBI nude and SCID mice. The results showed that in 6 of 6 human tumor cell lines studied, TD50S for SCID mice were 2.4 to 200 times lower than that of nude mice (significant in 5 cell lines). In contrast, in 2 of 3 murine tumors, TD50S in WBI SCID mice were significantly higher than that found in nude mice. When SCID and nude mice received WBI, TD50S were lower than those of nonirradiated animals in 5 of 5 xenografts (significant in 2 cell lines for nude mice and in 5 cell lines for SCID mice). We concluded that WBI SCID mice are significantly better recipients of human tumor xenografts than nude mice. There is a factor of 10-1625 gain in TD50S in favor of the WBI SCID mice when compared to nonirradiated nude mice. WBI has, however, an important effect on SCID mice which may suggest a detectable residual immunoreactivity, perhaps due to natural killer cells. These data demonstrate that WBI SCID mice are better models for human tumor transplantation that nude mice and, although WBI at 6 Gy suppressed significantly the immune system of nude mice, a certain level of immunoreactivity against xenografts is still maintained.
Taghian
A
A
Edwin L. Steele Laboratory of Radiation Biology, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston 02114.
Budach
W
W
Zietman
A
A
Freeman
J
J
Gioioso
D
D
Ruka
W
W
Suit
H D
HD
D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology; D002460:Cell Line; D003110:Colonic Neoplasms / Q000473:pathology; D005260:Female; D005354:Fibrosarcoma / Q000473:pathology*; D005909:Glioblastoma / Q000473:pathology; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000473:pathology*; D009374:Neoplasms, Experimental / Q000473:pathology*; D009447:Neuroblastoma / Q000473:pathology; D012509:Sarcoma / Q000473:pathology; D013045:Species Specificity; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured