maltose-tetrapalmitate and Adenocarcinoma

The nature of spleen cells in Fischer rats bearing a large size (greater than 1 cm diameter) mammary adenocarcinoma 13762A (MAC) which block the immunostimulating capacities of MTP2 (a synthetic immunomodulator) and suppress proliferation in vitro of splenic T and B lymphocytes by their respective mitogens was investigated. Splenic macrophages were recognized as the suppressor cells by (a) restoration of mitogenic responses by depletion of macrophages from spleen cell suspensions and (b) continued suppressor activity in spleen cell suspensions of tumor bearers devoid of viable T lymphocytes. Macrophage contact with T lymphocytes was required for the inhibition of T lymphocyte proliferation by concanavalin A as shown by (a) the absence of suppressor activity in supernatants derived from cultured suppressor macrophages, (b) lowering of the suppressor activity of intact macrophages after treatment with neuraminidase, (c) lowering of the suppressor activity of macrophages by addition of red cells to spleen cultures of tumor bearers indicating red cell interference with macrophage-T cell interaction and (d) lack of inhibiting action of suppressor macrophages on allogenic T lymphocyte proliferation showing macrophage T cell recognition for suppression. Animals bearing a large size tumor exhibited spleen hypertrophy and an increase in macrophage: lymphocyte ratio and a decrease in red cell: lymphocyte ratio. Splenic macrophages did not appear to be implicated in blocking antitumor immunity induction since (a) suppressor macrophages were absent in spleens during the inductive phase of the immune response and (b) MAC implanted in allogenic Wistar rats grew to about 2 cm diameter, induced splenic suppressor macrophages but the tumor was later rejected by the animals. Collectively the results suggest that suppressor macrophages are the result of increasing tumor volume rather than its cause.

Topics: Adenocarcinoma; Animals; Female; Glycolipids; Immune Tolerance; Indomethacin; Lymphocyte Activation; Macrophages; Mammary Neoplasms, Experimental; Rats; Rats, Inbred F344; Spleen

The effectivenss of maltose tetrapalmitate (MTP) as an antitumour immune adjuvant was verified by its comparison with other known immunopotentiators, namely BCG, Corynebacterium parvum, levamisole and pyran copolymer. Copenhagen x Fisher 344/CRBL F1 hybrid male rats inoculated s.c. with the Dunning R3327A prostatic adenocarcinoma were used as the test system. All animals treated with immunoadjuvants showed a delay in tumour appearance and inhibition of early tumour growth. MTP was found to be the most effective, followed by levamisole, BCG, pyran copolymer and C. parvum in order of decreasing efficacy. Intratumoral treatment of small or large s.c. tumours with BCG, MTP and C. parvum was ineffective in our cases. However, this treatment was effective with MTP and BCG if they were used against a differentiated form of R3327 tumour. MTP and levamisole were found to be equally effective when given orally in drinking water. Experiments involving surgical excision of tumours followed by MTP therapy in two s.c. implanted animal tumour models (viz. a poorly immunogenic ascites mammary carcinoma 13762 in Fisher 344/CRBL rats, and an SV40 virus-induced sarcoma of low immunogenicity in Syrian hamster) showed beneficial effects of MTP on local tumour recurrence and tumour growth. Pre- and postoperative MTP treatment was at least as effective as postoperative MTP treatment alone.

Topics: Adenocarcinoma; Adjuvants, Immunologic; Animals; Bacterial Vaccines; BCG Vaccine; Dose-Response Relationship, Immunologic; Glycolipids; Levamisole; Male; Maltose; Neoplasm Recurrence, Local; Neoplasms, Experimental; Palmitates; Postoperative Period; Propionibacterium acnes; Prostatic Neoplasms; Rats; Rats, Inbred Strains