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Biomedical subjects

E Ribi

Publications and source records attributed to E Ribi.

At least 19 recordsLinked to original sources
PubMed1979

Intralesional immunotherapy of malignant melanoma with mycobacterium smegmatis cell wall skeleton combined with trehalose dimycolate (P3).

The clinical efficacy of intralesional immunotherapy utilizing Mycobacterium smegmatis cell wall skeleton (CWS) and trehalose dimycolate attached to oil droplets was investigated in 15 patients with advanced malignant melanoma. Patients received 300 microgram to 1050 microgram of the CWS combined with one-half that amount of trehalose dimycolate every 1 to 2 weeks for a total of 8 treatments. Therapy was continued if regression of injected lesions only occurred. Therapy was discontinued if regression of noninjected disease also occurred. Six of the 15 patients had regression of at least one injected lesion. Four of these 6 patients also had regression of noninjected disease lasting 4+, 6, 16 and 18+ months. Response was highly related to immune status. Six (83%) of 7 patients who reacted to one of a battery of skin tests responded. All 8 patients who did not react to skin tests failed to respond to therapy. There was no correlation of response with sex, prior therapy, disease-free interval or presence of visceral disease. Mycobacterial CWS and trehalose dimycolate is an effective immunotherapeutic agent. Additional studies of purified immunoadjuvants are warranted.

Cell Wall↗
PubMed1979

[Immunotherapy with BCG and mycobacterial fractions and its use in bronchogenic carcinoma (author's transl)].

Animal experiments at the Nat. Cancer Inst. have established that only intra-tumorous application of BCG vaccine has a lasting immunotherapeutic effect on transplantable tumours. However, clinical observations have proved that BCG immunotherapy by the intra-tumorous route increases the incidence of complications, such as allergic reactions and generalized spread of BCG, to an unacceptable level. Ribi has produced a vaccine from mycobacterial fractions which is low in protein and which, as proved in clinical pilot studies in cases of melanoma and cancer of the breast, is so well tolerated that it can be injected into the tumour. Since bronchogenic carcinoma is in the majority of cases inoperable, but, on the other hand, can be reached directly via the bronchoscope or the perthoracic route a pilot study with the Ribi vaccine was started in patients with lung cancer. The preliminary results are reported.

BCG Vaccine↗
PubMed1978

Glucan: attempts to demonstrate therapeutic activity against five syngeneic tumors in guinea pigs and mice.

Animals with established syngeneic tumor transplants were treated with glucan to study the therapeutic potential of this agent under well-defined experimental conditions. The tumors used were a guinea pig hepatoma, 2 murine fibrosarcomas, a murine melanoma, and a murine adenocarcinoma. All tumors were syngeneic to the host. Living BCG, administered directly into guinea pig tumors, cured all animals, whereas glucan, administered under the same conditions, had no significant antitumor activity. Neither BCG nor glucan, when administered iv, was active against the guinea pig hepatoma. An emulsion prepared with endotoxin, a fraction of mycobacteria related to cord factor, and mineral oil when administered intratumorally was also effective in treatment of line 10 tumor. A similar emulsion, in which glucan was substituted for endotoxin, was inactive, intralesional, ip, or iv administration of glucan was ineffective against the murine tumors. Previous reports of glucan-induced activity against a B16 murine melanoma were not confirmed. BCG was tested against the 2 murine fibrosarcomas and, when given either intratumorally or iv, was found to be effective against one of them.

Animals↗
PubMed1978

Intratumor chemoimmunotherapy with mitomycin C and components from mycobacteria in regression of line 10 tumors in guinea pigs.

Intratumor chemotherapy with the use of mitomycin C and/or immunotherapy caused regression of line 10 carcinomas in strain 2 guinea pigs and resulted in development of tumor-specific immunity. The immunotherapeutic preparation consisted of oil-in-water emulsions containing Mycobacterium cell walls or residues of cell walls termed cell wall skeletons. The latter preparations were combined with trehalose dimycolate, which was isolated by microparticulate chromatography from whole cells of mycobacteria. Reducing mitomycin C to a single intratumor injection of 50 microgram produced little necrotizing effect and a mean tumor regression rate of 17%. Intratumor immunotherapy 1 day after treatment with 50 microgram of mitomycin C resulted in regression of 90% of the treated tumors as compared to mean regression rates of 30 to 50% for immunotherapy alone. In addition, chemoimmunotherapy was more effective than either chemotherapy or immunotherapy alone in producing regression of relatively large, as well as smaller, tumors.

Animals↗
PubMed1977

Immunotherapy of a guinea pig hepatoma with living BCG: a frozen liquid and a lyophilized preparation are equally active.

A freeze dried preparation of BCG with a low ratio of living to dead organisms (LV) was compared to a frozen liquid preparation with high viability (HV) for its ability to eradicate established dermal tumors and microscopic lymph node metastases in guinea pigs. The cure rate achieved by the intralesional injection of LV-BCG did not differ significantly from that of HV-bcg when similar numbers of viable organisms were injected.

Animals↗
PubMed1976

Immunotherapy with nonviable microbial components.

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.

Animals↗
PubMed1976

Cutaneous granulomatous response to BCG cell walls with reference to cancer immunotherapy.

A chronic inflammatory response produced by cell walls of Mycobacterium bovis strain BCG associated with microscopic oil droplets (BCG CW-O) was studied with reference to the tumor-regressing ability of this preparation. When BCG CW-O was injected intradermally in the footpads of guinea pigs, intense inflammation developed at the site of injection and in the draining popliteal lymph node. This was characterized histologically as granulomatous inflammation. The intensity of the response was related to the dose of BCG CW-O. Cell walls without oil produced the same type of inflammation but much less in degree. Data are presented that demonstrate the immunological nature of this response and classify it as a cell-mediated immune reaction. Ramifications of this chronic inflammatory reaction occurring at the site of a tumor are discussed.

Animals↗
PubMed1976

Delayed hypersensitivity and granulomatous response after immunization with protein antigens associated with a mycobacterial glycolipid and oil droplets.

A myocardial glycolipid (P3) mixed with protein antigens in oil-in-water emulsion induced lasting delayed hypersensitivity (DH) and granulomatous inflammation after intradermal injection into guinea pigs. This did not occur when P3 and bovine serum albumin (BSA) were given in Freund's incomplete adjuvant. The oil-in-water emulsions consisted of microscopic oil droplets suspended in aqueous medium. By separating oil and aqueous phases from BSA + P3 emulsion it was shown that antigen retained with oil droplets led to DH and granuloma formation. The association of antigen with oil droplets was P3 dependent and was quantitated with 125I-labeled BSA. The same phenomenon occurred with 125I-labeled rabbit gamma-globulin (RGG) + P3 emulsion. Fluorescein-conjugated RGG was observed in a particulate state within or on oil droplets in emulsion containing P3. These physical characteristics of antigen + P3 emulsion appeared to be important for immunogenicity.

Animals↗
PubMed1975

Immunotherapy of cancer: tumor suppression and regression by cell walls of Mycobacterium phlei attached to oil droplets.

Components of mycobacterial cell wall(s) (CW) attached to oil droplets were evaluated for their ability 1) to inhibit the growth of line-10 tumor transplants in the skin of syngeneic guinea pigs when inoculated together with 10(6) tumor cells (suppression experiments) and 2) to regress established 7-day-old intradermal tumors and eradicate microscopic lymph node metastases upon injection into the tumors (regression experiments). CW and cell-wall skeleton (CWS) preparations from Mycobacterium phlei, a fast-growing saprophyte of group IV of the atypical mycobacteria, suppressed tumor growth in essentially all animals when 37.5-mug doses were administered; at a dose of 300 mug, they cured 50-60% of the animals in regression tests. The addition of 300 mug of a purified trehalose mycolate, isolated from M. tuberculosis strain Aoyama B, to 300 mug M. phlei CW or CWS preparations significantly increased their tumor regressive potency to provide cure rates to about 90%. Because M. phlei can be propagated more readily, it can be used advantageously in place of BCG to prepare stable, non-living immunologic adjuvants of defined composition and consistently high potency to meet the need for standards with minimal residual malignant disease.

Animals↗