IMMUNOTHERAPY WITH BIOCHEMICALLY DISSOCIATED FRACTIONS OF PROPIONIBACTERIUM ACNES IN A MURINE OVARIAN-CANCER MODEL

  • 1 January 1984
    • journal article
    • research article
    • Vol. 44  (5) , 1871-1875
Abstract
The antitumor effect of 2 strains of P. acnes (PAI and PAII) and chemically derived fractions from the whole bacterial cell were studied using a murine ovarian teratocarcinoma (MOT) model. When injected i.p. in high doses (700-1400 .mu.g/mouse), both strains produce survival of a significant proportion of tumor-bearing mice (30-90%). On a weight to weight basis PAI was significantly more effective than PAII. PAI and PAII were extracted using pyridine, which yielded 4 fractions, i.e., pyridine-extracted strains PAI and PAII (PA-PEI and PA-PEII, respectively) which are composed of the cell wall material extracted by pyridine, and the residues of PA-PEI and PA-PEII (PA-RI and PA-RII, respectively) which are composed of the residue material following the chemical extraction. The chemical composition of PA-PEI was different from that of PA-PEII (the latter had proportionately 3 times as many carbohydrates and 1/3 of the protein content of the former) and so were their antitumor properties in the MOT model. PA-PEI had markedly reduced antitumor effect when compared to the untreated cell on a per weight basis. Curability was only seen when using a high dose (1400 .mu.g/mouse). The cell wall components extracted by pyridine from PAII (PA-PEII) had powerful antitumor effects, i.e, > 50% of mice given 1400-.mu.g injections survived. The material contained in PA-PEII was further fractionated on the basis of its organic solubility in chloroform:methanol solvent. The water-soluble and solvent-insoluble fraction retained most of the antitumor effects of PA-PEII, while the water-insoluble and solvent-soluble fractions were only moderately effective, suggesting that the active moiety(ies) was associated with the nonlipid components of this fraction. Both residue fractions (PA-RI and PA-RII) were as effective on a per weight basis in controlling the growth of 105 tumor inoculum as were whole untreated cells. Periodate oxidation of Pa-RI resulted in complete loss of its antitumor effects. When surviving mice that had no evidence of tumor persistence following a tumor challenge (105 MOT cells) and i.p. treatment with PA were subsequently rechallenged with 104 tumor cells, survival was significantly prolonged, as compared to tumor-challenged (104 MOT) naive mice. In addition, 10-20% of these rechallenged mice had complete eradication of the tumor inoculum (no evidence of disease for > 120 days). Mice previously exposed to PA are probably still capable of resisting the growth of a lethal tumor rechallenge given > 50 days after the primary inoculation. Studies to elucidate the immunological basis for the rejection of a tumor rechallenge are currently under way.

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