Transplantation of Human Tumour to Immune Deprived Mice Treated with Anti-thymocyte Serum

Abstract

Summary.-Five out of 18 primary explants of human carcinomata obtained at operation have been grown progressively for a minimum of one month in thymectomized, x-irradiated mice reconstituted with syngeneic bone marrow and subsequently treated also with anti-thymocyte serum. All the tumours which proliferated were of gastrointestinal origin, growing locally but not metastasizing although direct invasion of the ribs occurred in one case. No implanted breast carcinomata grew in this system. THE aim of the present experiments was to determine whether immunedeficient mice provided a suitable environment for the progressive growth of implanted human carcinomata.Numerous methods of heterotransplantation have been described and reviewed (Chesterman, 1959). It is generally accepted that cell mediated immunity is largely responsible for xenograft rejection and that anti-thymocyte serum (James, 1967) and x-irradiation (Toolan, 1955) are effective immunosuppressants in this context. Thymectomy appears to enhance the action of anti-thymocyte serum (ATS) on first generation tumour graft survival in mice (Jeejeebhoy, 1967;Phillips and Gazet, 1970). Thymectomy combined with irradiation and bone marrow reconstitution to produce immune deprived mice is now a well known immunosuppressive regimen. A relatively more permanent immune impairment is produced in deprived mice than with ATS treatment alone, which is specific for T lymphocyte depletion and dependent on serum potency and the period of its administration. In these bone marrow reconstituted mice, a lymphoid population of cells will eventually develop so that ATS administration would be an added precaution against the cell mediated response returning. In order to keep ATS toxicity to a minimum, low doses of serum were injected twice weekly until the graft seemed to have established. MATERIALS AND METHODSMale and female adult A2G mice, inbred for at least 45 generations, were used. The mice were weaned and separated according to sex at 3 weeks of age. Female New Zealand white rabbits weighing between 2-5 and 3-5 kg were employed for ATS preparation.Two ml of a thymocyte suspension prepared from the thymuses of 8 A2G mice were injected intravenously through the ear vein of each rabbit according to the method of Levey and Medawar (1966

Human breast-cancer xenografts in immune-suppressed mice

“…If serial transplantation is considered a necessary characteristic of a successful xenograft, published take rates vary from zero (Gershwin et al, 1977) to 1355% (Giovanella et al, 1976) using nude mice. No transplantable human breast-cancer xenografts have previously been reported in artificially immune-suppressed mice, in spite of several attempts (Detre & Gazet, 1973;Berenbaum et al, 1974). That both the nude mouse and the immune-suppressed mouse will readily accept xenografts of many other human tumours is well known (Shimosato et al, 1976;Stanbridge et al, 1975;Giovanella et al, 1976).…”

Sequestration of Macrophages in Growing Tumours and its Effect on the Immunological Capacity of the Host

“…Similarly, good, poor and no growth occurred indiscriminately among ovarian carcinomata that varied from well differentiated to anaplastic, and 4 out of 7 benign ovarian tumours also grew (Table III) a.J2 were discontinued. There would therefore seem to be little difficulty in serially transplanting tumours that grow well in the first instance, as noted also by Cobb (1973) and Detre and Gazet (1973).…”

“…However, caution is required in view of the finding of Cobb (1973) and Detre and Gazet (1973) that the frequency of mitoses in human tumours examined some months after transplantation to immunosuppressed mice was usually higher than in the primary tumour. It is not known whether this was due to these relatively small tumour masses being better vascularized than the larger primaries from which they were derived, or whether selection of rapidly growing cells had occurred during the 3-8 months sojourn in the xenogeneic host.…”

The monolayer and organ culture of human colorectal carcinomata and the associated "normal" colonic mucosa and their production of carcinoembryonic antigens

“…Indeed, the establishment of the tumour cell cultures proved rather difficult, although some long-term (7 month) survivals were achieved. This contrasts with the ready transplantation of primary human colorectal carcinomata into suitably immunologically deprived experimental animals (Cobb, 1973;Detre and Gazet, 1973). Utilizing this latter procedure and harvesting cells from such tumours did not yield cell preparations from which cells grew or were maintained more readily.…”