Effect of cyclosporin A on the growth and spontaneous metastasis of syngeneic animal tumours

Abstract

Summary.-Cyclosporin A (Cy A), a novel immunosuppressive agent with apparently selective inhibitory effects on T lymphocytes and little myelotoxicity, was tested for its effects on a variety of syngeneic animal tumours including sarcomas, carcinomas and a T-cell lymphoma. Cy A, given orally or parenterally in repeated doses, had no effect on the growth rates of any of the tumours tested, but a highly significant effect on metastasis was seen in many cases. All the sarcomas examined in both rats and mice, and also the lymphoma, showed a marked increase in their metastases, in some cases even when administration of Cy A was delayed until after excision of the "primary" tumour implants. In contrast no effect of Cy A on metastasis was observed in animals bearing poorly immunogenic mammary or squamous-cell carcinomas. The metastases developing in Cy A-treated animals, when transplanted into normal syngeneic animals, showed no evidence of enhanced metastatic potential compared with their"parent" tumours.

Effect of host immune status on the spontaneous metastasis of cloned cell lines of the 13762NF rat mammary adenocarcinoma

“…Using this assay, the only obvious effect of CyA was a reduction in the number of FcR+ cells infiltrating the tumour. Similar observations have been made by Eccles et al (1980), who used both mouse and rat fibrosarcomas.…”

“…Recent reports have now established that the influence of CyA on the immune system is much more extensive (Kunkel & Klaus, 1980;Klaus, 1981). Our data showed that at (Eccles et al, 1980). Using this assay, the only obvious effect of CyA was a reduction in the number of FcR+ cells infiltrating the tumour.…”

“…Effect of excision of the tumour on metastasis It is possible that the increased tumour burden that results from the continued presence of an s.c. (Gilbert & Kagan, 1976 (Eccles et al, 1980). To test the effect of this drug on 13762NF adenocarcinoma 6/gb 9/9 4/9 5/9 0/9 0/9 -5 13.33 + 3.48 2/lOC R R 2/10 2/10 1/10 (thymus) 1/10 (mesentery) 1/10 (cervical) 2/10 (sub-axillary) -1 sham 21.44+4.17 4/9 5/9 6/9 1/9 0/9 0/9 -1 22.50+3.85 2/9 R R(1/9) 0/9 0/9 0/9 + 5 sham 21.72+4.42 4/9 9/9 8/9 6/9 3/9 3/9 (thymus)…”

2nd Gordon Hamilton Fairley Lecture

“…With oestrogen-dependent tumours, dormancy extending for very long periods can be detected by transplanting the tumours into noirmal recipients, in which no growth occurs, and then admininistering oestrogen, when macroscopic growth sets in. Noble & Hoover (1975), Eccles & Alexander (1975) and Eccles et al (1980) found that dormant metastases were common in chemically induced rodent sarcomas and lymphomas which did not metastasize frequently when transplanted to normal syngeneic animals, in which they can be "cured" by surgical removal of the primary implant and its draining node. When such tumours were allowed to grow for a set period before being excised surgically, dormant metastases, seeded from the primary implant before it was excised, were revealed as lung or distant lymph-node metastases after immunosuppression, especially that caused by Cyclosporin A (Eccles et al, 1980), long after surgery (Fig.…”

Comparison of the potential therapeutic effects of interleukin 2 or interleukin 4 secretion by a single tumour

“…In rodent tumour studies IL-2 Ley et al, 1991), (Golumbek et al, 1991) and y-IFN (Watanabe et al, 1989;)-secreting tumour cells have each been shown to induce protection against parental tumour cell challenge. In order to determine which of these therapeutic routes might be the more feasible, we have compared the properties of IL-2 and IL-4-secreting tumour cells in a single murine tumour, the transplantable fibrosarcoma, FS29 (Eccles et al, 1980). We have demonstrated that either IL-2, or IL-4-secreting cells show a poor ability to induce the rejection of admixed parental cells.…”