cord-factors and Liver-Neoplasms

Structural components of microorganisms have been studied for immunopotentiating effect with the aid of transplantable (line 10) tumors in syngeneic guinea pigs. Microbial components were associated with oil droplets, suspended in Tween-saline, and injected intralesionally. BCG cell walls, given in this way, produced regression and cure of 50-60% of established tumors, as did viable BCG. Lipid extraction markedly reduced the tumor-regressing potency of cell walls, but P3, a trehalose mycolate present in the extract, restored full activity to the cell wall residue. P3 alone was nonsensitizing and had no antitumor activity, but it enhanced the latter property of various other microbial products. For example, the cure rates produced by cell walls of M. tuberculosis, M. bovis, M. phlei, or M. smegmatis were enhanced from 20-60% to as much as 90% by addition of P3. P3 also conferred antitumor activity on products from unrelated microbes, such as cell walls of E. coli, and in combination with endotoxins from rough Re mutant salmonellae, it produced cure rates of up to 93%. These results suggest that P3 is essential to the immunopotentiating activity of mycobacteria and that it may be broadly applicable in immunotherapy of cancer with microbial agents.

Topics: Animals; Bacteria; BCG Vaccine; Carcinoma, Hepatocellular; Cell Wall; Cord Factors; Endotoxins; Escherichia coli; Glycolipids; Guinea Pigs; Immunotherapy; Liver Neoplasms; Mycobacterium; Mycobacterium bovis; Mycolic Acids; Neoplasm Transplantation; Neoplasms, Experimental; Salmonella; Transplantation, Homologous; Trehalose

A transplantable hepatocarcinoma of strain 2 guinea pigs was used as an experimental model for immunotherapy of cancer. 6,6'-Dideoxy-6,6'-bis-mycoloylamino-alpha,alpha- trehalose (TDNM) was found to be more effective in producing regression of transplantable line-10 tumours than 6,6'-di-O-mycoloyl-alpha,alpha-trehalose (TDM) when combined with 6-O-stearoyl muramyldipeptide (L18-MDP). TDNM showed potent antitumour activity in combination with synthetic lipid A of Escherichia coli (compound 506), but not with the lipid A analogues (GLA-59 and 60). As with the combination of MDP derivative and lipid A analogue, MDP derivatives conjugated with GLA-60 (GMD compounds) showed no tumour regression activity of line-10 cells in guinea-pigs.

Topics: Acetylmuramyl-Alanyl-Isoglutamine; Adjuvants, Immunologic; Animals; Antineoplastic Combined Chemotherapy Protocols; Cord Factors; Guinea Pigs; Lipid A; Liver Neoplasms; Liver Neoplasms, Experimental; Remission Induction

A vaccine containing non-living BCG and living tumour cells prevented the growth of 106 tumour cells introduced distally into the skin of guinea-pigs at the time of vaccination. A similar effect was achieved when living tumour cells of the vaccine were replaced by tumour cells pretreated with mitomycin C. The efficacy of the vaccine was significantly increased when cord factor was added to the vaccination mixture. The percentage of cures was about 88% (17 cases) in experiments in which the vaccine contained living tumour cells, 100% (10 cases) when mitomycin C-treated cells were used. The significance and implications of the above findings are discussed.

Topics: Animals; BCG Vaccine; Carcinoma, Hepatocellular; Cell Line; Cell Transformation, Neoplastic; Cord Factors; Depression, Chemical; Glycolipids; Guinea Pigs; Immunotherapy; Liver Neoplasms; Mitomycins; Neoplasms, Experimental; Trehalose