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Immunotherapy of experimental cancer by intralesional injection of emulsified nonliving mycobacteria: comparison of Mycobacterium bovis (BCG), Mycobacterium phlei, and Mycobacterium smegmatis.

Mycobacterium bovis (BCG), Mycobacterium phlei, and Mycobacterium smegmatis were each tested in emulsified form for their potency to cause regression of transplants of a syngeneic murine fibrosarcoma and of a syngeneic guinea pig hepatoma. On a weight basis, M. phlei and M. smegmatis were as effective as BCG in causing tumor regression. M. phlei and M. smegmatis were comparable to BCG in provoking delayed cutaneous hypersensitivity reactions in guinea pigs sensitized to M. phlei or M. smegmatis. In BCG-sensitized guinea pigs, M. phlei and M. smegmatis provoked weaker delayed cutaneous hypersensitivity reactions than did BCG. Purified protein derivative of M. tuberculosis was more active in eliciting delayed cutaneous hypersensitivity in BCG-sensitized guinea pigs than in animals sensitized with M. phlei or M. smegmatis.

Animals↗

Immunotherapy of guinea pigs with a transplanted hepatoma: comparison of intralesionally injected emulsions containing heat-killed Nocardia rubra, Mycobacterium bovis (BCG) and Mycobacterium phlei.

Heat-killed cells of Mycobacterium bovis (BCG), Mycobacterium phlei and Nocardia rubra were each tested in emulsified form for their ability to cause regression of established dermal transplants and lymph node metastases of a syngeneic hepatocarcinoma in guinea pigs. On a weight basis, BCG was superior to N. rubra in causing tumor regression. Under the conditions tested N. rubra was inferior to M. phlei in its antitumor activity. M. phlei and BCG were approximately the same in their therapeutic potency. In BCG-sensitized guinea pigs, N. rubra provoked a weaker delayed cutaneous hypersensitivity (DCH) reaction than did BCG. In N. rubra-sensitized guinea pigs, BCG provoked a weaker DCH reaction than did N. rubra. Purified protein derivative of M. tuberculosis was more active in eliciting DCH in BCG-sensitized guinea pigs than in animals sensitized with N. rubra.

Animals↗

Intralesional injection of interferon gamma affects reactive proliferation of astrocytes in the neonatal rat brain. A preliminary study of the age-dependent effect.

Following a mechanical lesion of the left cerebral hemisphere, newborn male rats received a single injection of recombinant rat interferon gamma (IFN gamma) into the lesion cavity at doses of 5, 50 and 500 U. One or two days after the injury the rats were injected with 3H-thymidine. Brain sections were immunostained for glial fibrillary acidic protein (GFAP), subjected to autoradiography and examined microscopically to record proliferating GFAP-immunopositive (GFAP+) astrocytes labeled with 3H-thymidine. Following the intermediate 50 U dose of IFN gamma, numbers of GFAP+ astrocytes and of their mitoses on day 1 after injury were significantly higher than in controls. Nevertheless, the astrocyte labeling index remained at the control level. Injections of the minimal 5 U or the maximal 500 U doses of IFN gamma had no effect on that day. On day 2, however, each of the three doses evoked a statistically significant but dose-independent reduction of the labeling index without similar changes in total number of GFAP+ astrocytes or in numbers of their divisions. The changes appear to indicate a non-linear relation between the intensity of reactive behaviour of astrocytes and the amount of IFN gamma injected into the lesion area. On the basis of previous publications, IFN gamma effects on the astrocyte reactivity are discussed as being age-dependent.

Animals↗

Cellular events accompanying regression of skin recurrences of breast carcinomas treated with intralesional injections of natural interferons alpha and gamma.

Cutaneous recurrences of breast carcinomas were treated with 10 i.l. injections of nIFNs alpha and gamma delivered in combination (7 lesions) or singly (11 with nIFN-alpha, one with nIFN-gamma). Histologically confirmed complete regressions occurred in 5 of 7 lesions treated with nIFN-alpha/nIFN-gamma and in 5 of 11 recurrences injected with nIFN-alpha alone. In all cases specimens were obtained before and after therapy. In addition, in some cases (4 treated with nIFN-alpha/nIFN-gamma, 2 with nIFN-alpha, one with nIFN-gamma) multiple recurrences were injected simultaneously and were excised 24 h after 1, 3, and 10 injections and 21 days after completion of therapy. The main findings observed in the treated lesions undergoing complete and partial regressions included: (a) inhibition of mitotic activity and up-regulation of antigenic expression (mammary epithelial membrane antigen, intercellular adhesion molecule 1, HLA-DR) by the carcinoma cells; (b) activation of macrophages and dendrocytes with marked expression of HLA-DR and HLA-A,B,C; (c) infiltration of the dermis and tumors by activated T-lymphocytes (CD3+, CD4+, CD8+); (d) questionable participation by B-lymphocytes and natural killer cells; (e) activation of endothelium with enhancement of antigenic expression (intercellular adhesion molecule 1, HLA-DR), procoagulant activity, and vascular permeability. The responses elicited by nIFN-alpha/nIFN-gamma were greater than those caused by either IFN used alone. It appears that in these patients the IFNs exerted an antiproliferative action and potentiated a cell-mediated immunological response liminally present in the neoplastic tissues prior to therapy.

Administration, Cutaneous↗

Histological changes caused by intralesional injection of a streptococcal preparation into bladder cancer.

OK-432, a lyophilized preparation of Streptococcus pyogenes, was cystoscopically injected into bladder cancer to destroy cancer cells and to prevent recurrences. Marked reactions occurred such as stromal edema, vascular dilation, cancer cell exfoliation, and polymorphonuclear cell infiltration, succeeded by monocyte and lymphocyte infiltration with occasional lymph follicle formation. Cancer cells were sometimes intermingled in microscopic necrotic foci. Foamy granuloma was another characteristic finding. The postoperative follow-up study showed a significantly low recurrence rate.

Aged↗

Tumor regression after intralesional injection of mycobacterial components emulsified in 2,6,10,15,19,23-hexamethyl-2,6,10,14,18,22-tetracosahexaene (squalene), 2,6,10,15,19,23-hexamethyltetracosane (squalane), peanut oil, or mineral oil.

The influence of mineral oil, squalane, squalene, or peanut oil on the antitumor activity of emulsified Bacillus Calmette-Guérin cell walls or emulsified trehalose-6,6'-dimycolate was studied in mice, each with an established transplant of a syngeneic fibrosarcoma. Each animal received an intratumoral injection of Bacillus Calmette-Guérin cell walls (0.6 mg/mouse) or trehalose-6,6'-dimycolate (0.1 mg/mouse) emulsified in 1 to 10% oil. Emulsions of squalene or squalane but not peanut oil were effective substitutes for mineral oil as carriers of Bacillus Calmette-Guérin cell walls in the treatment of the tumor. Trehalose-6,6'-dimycolate was therapeutically active when it was incorporated in any of these four oils. The number of animals in which tumor regressed completely depended on the concentration of oil in the emulsion.

Animals↗