Kazuhisa Sugimura

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

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, Hodgkins disease, and other neoplastic diseases and that this agent operates without any significant complications.

The adjuvant activity of synthetic N-acetylmuramyl-dipeptide: Evidence of initial target cells for the adjuvant activity

Abstract MurNAc- l -Ala- d -isoGln ( N -acetylmuramyl- l -alanyl- d -isoglutamine, MDP), a synthetic compound, acts as an adjuvant on the humoral immune response and on the T cell-mediated immune response. In this report, we attempted to directly demonstrate the initial target cells of MDP for its adjuvant activity in vitro by using cell separation procedures. It was demonstrated that MDP enhanced the immune response following direct interaction with antigen-stimulated T and B lymphocytes, but nonstimulated lymphocytes, shortly after triggering by antigen, and that there was no macrophage requirement for MDP to elicite the adjuvant action in the primary anti-SRBC PFC response in vitro . It has also been demonstrated that the adjuvant activity of MDP is due to an enhancing effect which is different from the possible mitogenic activity to spleen cells and MDP replaces neither a function of macrophages, which is substituted by 2-mercaptoethanol nor a helper function of T cells.

Macrophage dependency of T-lymphocyte mitogenesis by Nocardia rubra cell-wall skeleton.

The mitogenic activity of the cell‐wall skeleton (CWS) of Nocardia rubra on purified splenic T‐cells (thymus‐derived lymphocytes) was investigated. N. rubra CWS showed remarkable mitogenic activity on normal spleen cells of C57BL/6J mice at concentrations ranging from 10 to 100 μg per milliliter of culture medium, while, on purified splenic T‐cells, N. rubra CWS did not act as a mitogen at any concentration. However, mitogenic activity of N. rubra CWS on T‐cells was restored if purified splenic T‐cells were reconstituted with X‐irradiated peritoneal exudate cells (macrophages). The above results suggest the necessity of macrophages for T‐lymphocyte activation by N. rubra CWS as well as PHA‐P or Con A.