IMMUNOTHERAPY OF CANCER WITH CELL WALL SKELETON OF MYCOBACTERIUM BOVIS‐BACILLUS CALMETTE‐GUÉRIN: EXPERIMENTAL AND CLINICAL RESULTS

Abstract

Adjuvant and antitumor activities of CWS prepared from cells of mycobacteria, nocardia, and corynebacteria were examined. Oil-attached CWS of M. bovis BCG (BCG-CWS) stimulated the generation of cell-mediated cytotoxic effector cells in mice. Tumor growth was suppressed in mice inoculated intradermally with a mixture of oil-attached CWS and living tumor cells. Systemic and specific tumor immunity was demonstrated in mice in which tumor growth was suppressed. Tumor growth was also suppressed by oil-attached CWS of BCG or N. rubra in autochthonous autografts of spontaneous mammary adenocarcinoma and methylcholanthrene-induced fibrosarcoma in mice. The intravenous injection of oil-attached BCG-CWS prevents the appearance of lung cancer in rabbits by the instillation of chemical carcinogens. It was also shown that treatment with oil-attached BCG-CWS was able to elevate the immunologically depressed state of tumor-bearing mice to a normal level, as determined by a cell-mediated cytotoxicity assay that empolyed chromium release as the standard. Preliminary results suggest that oil-attached BCG-CWS is useful as an immunotherapeutic agent for both lung cancer and for malignant melanoma, leukemia, Hodgkin's disease, and other neoplastic diseases and that this agent operates without any significant complications.

Simultaneous Blocking of Human Toll-Like Receptors 2 and 4 Suppresses Myeloid Dendritic Cell Activation Induced byMycobacterium bovisBacillus Calmette-Guérin Peptidoglycan

“…The results are consistent with the reported immunopotentiating activity of BCG CWS, which acts as a potent immune adjuvant sufficient to promote antibody production, induce CTL proliferation, and exert antitumor activity in immunoadjuvant therapy (2,47,49). BCG CWS is a complex consisting of mycolic acids, arabinogalactan, and peptidoglycan (PGN) (2), and which part is responsible for BCG CWS activity has not been determined (Fig.…”

Immunotherapy of autochthonous rat methylcholanthrene-induced sarcomas with a mixture of allogeneic tumor cells and BCG-CWS.

“…There are many reports on non-specific immunotherapy of cancer, especially on the effect of BCG. The application of BCG-CWS was also described (Ribi et al 1978;Yamamura et al 1976). The suppression of autochthonous transplantation of MCA-induced fibrosarcomas in mice was observed when a piece of the tumor with oil-attached BCG-CWS was autotransplanted (Tokuzen et al 1975 Kronman et al (1970) reported that immunization with living syngeneic tumor cells retarded the growth of transplanted tumors in strain-2 guinea pig hepatoma system.…”

Innate immunity in breast carcinoma.

“…For example, mice implanted with the immunogenic syngeneic mammary carcinoma MC2 showed enhanced resistance to tumor development only when pretreated long term with BCG, whereas mice injected with BCG and simultaneously implanted with MC2 cells showed decreased resistance to the tumor (Vaage 1983). Results in other studies were dependent on the dose, the administration protocols and the BCG preparation used, demonstrating tumor regression in some cases but accelerated rates of tumor growth and early death in others (Likhite 1976, Yron et al 1975, Yamamura et al 1976.…”