Summary
The clinical toxicity and efficacy of intralesional immunotherapy with a nonviable mycobacterial vaccine consisting of Mycobacterium smegmatis cell wall skeleton (CWS) and trehalose dimycolate (P3) attached to oil droplets was investigated. Thirty-four patients received a total of 192 infections, the doses ranging from 150 μg CWS and 75 μg P3 to 1200 μg CWS and 600 μg P3. Treatment was well tolerated. Mild fever and chills occurred in approximately 70% of treatments. There was no discernible effect on hematologic, renal, or hepatic parameters.
Of the 34 patients, CWS/P3 therapy was clinically effective in seven with metastic malignant melanoma in causing regression of the infected lesion. Four of these seven patients also had an objective response of noninjected lesions by over 50%. Pulmonary metastatis responded in one patient. CWS/P3 therapy caused an increase in the skin test response of 14 of the patients to CWS antigen. There was no measurable consistent change in reactivity to recall antigens, T or B cell populations, PHA response, or serum proteins associated with the intralesional CWS/P3 therapy.
Nonviable CWS/P3 is an effective agent for human immunotherapy. This and other purified bacterial components warrant continued investigation as single agents in clinical immunotherapy trials.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Aungst, C. W., Sokal, J. E., Jager, B. V.: Complications of BCG vaccination in neoplastic disease. Ann. Intern. Med. 82, 666 (1975)
Azuma, I., Ribi, E. E., Meyer, T. J., Zbar, B.: Biologically active components from mycobacterial cell walls. I. Isolation and composition of cell wall skeleton and component P3. J. Natl. Cancer Inst. 53, 95 (1974)
Bast, R. C., Zbar, B., Borsos, T., Rapp, H. G.: BCG and cancer. N. Engl. J. Med. 290, 1413, 1458 (1974)
Bornstein, R. S., Mastrangelo, M. J., Sulit, H., Chee, D., Yarboro, J. W., Prehn, L., Prehn, R. J.: Immunotherapy of melanoma with intralesional BCG. Natl. Cancer Inst. Monogr. 32, 213 (1973)
Boyum, A.: Separation of leucocytes from blood and bone marrow. Scand. J. Clin. Lab. Invest. [Suppl.] 21, 97 (1968)
Eilber, F. R., Morton, D. L., Holmes, E. C., Sparks, F. C., Ramming, K. P.: Adjuvant immunotherapy with BCG in treatment of regional lymph-node metastasis from malignant melanoma. N. Engl. J. Med. 294, 237 (1976)
Gray, G. R., Ribi, E., Granger, D., Parker, R., Azuma, I., Yamamoto, K.: Immunotherapy of cancer: Tumor suppression and regression by cell walls of Mycobacterium phlei attached to oil droplets. J. Natl. Cancer Inst. 55, 727 (1975)
Jondal, M., Holm, G., Wigzell, H.: Surface markers on human B. and T lymphocytes. I. A large population of lymphocytes forming nonimmune rosettes with sheep red blood cells. J. Exp. Med. 186, 207 (1972)
Krown, S. E., Hilal, E. Y., Pinsky, C. M., Hirshaut, Y., Wanebo, H. J., Hanson, J. A., Huvos, A. G., Oettgen, H. F.: Intralesional injection of the methanol-extracted residue of Bacillus Calmette-Guérin (MER) into cutaneous metastasis of malignant melanoma. Cancer 42, 2648 (1978)
Mastrangelo, M. J., Bellet, R. E., Berkelhammer, J., Clark, W. H.: Regression of pulmonary metastatic disease associated with intralesional BCG therapy of intracutaneous melanoma metastasis. Cancer 36, 1305 (1975)
McKhann, C. F., Hendrickson, C. G., Spitler, L. E., Gunnarsson, A., Banerjee, D., Nelson, W. R.: Immunotherapy of melanoma with BCG — two fatalities following intralesional injection. Cancer 35, 514 (1975)
McLaughlin, C. A., Strain, S. M., Bickel, W. D., Goren, M. B., Azuma, K., Milner, K., Cantrell, J. L., Ribi, E.: Regression of line-10 hepatocellular carcinomas following treatment with water-soluble, microbial extracts combined with trehalose or arabinose mycolates. Cancer Immunol. Immunother. 4, 61 (1978)
Mastrangelo, M. J., Sulit, H. L., Prehn, L., Bornstein, R. S., Yarboro, J. W., Prehn, R. T.: Intralesional BCG in the treatment of metastatic malignant melanoma. Cancer 37, 684 (1976)
Minden, P., McClutchy, J. K., Wainberg, M., Weiss, D. W.: Shared antigens between Mycobacterium bovis (BCG) and neoplastic cells. J. Natl. Cancer Inst. 53, 1325 (1974)
Morton, D. L., Eilber, F. R., Malmgren, R. A., Wood, W. C.: Immunological factors which influence response to immunotherapy in malignant melanoma. Surgery 68, 158 (1970)
Nathanson, L.: Use of BCG in the treatment of human neoplasms: A review. Semin. Oncol. 1, 337 (1974)
Snedecor, G. W., Cochran, W. G.: Statistical methods, 6th ed. Ames, Iowa: Iowa State Press
Ribi, E., Milner, K. C., Granger, D., Kelly, M. T., Yamamoto, K., Brehmer, W., Parker, R., Smith, R. F., Strain, S. M.: Immunotherapy with non-viable microbial components. Ann. N.Y. Acad. Sci. 227, 228 (1976)
Vosika, G. J., Schmidtke, J., Goldman, A., Ribi, E., Parker, R., Gray, G.: Intralesional immunotherapy of malignant melanoma with Mycobacterium smegmatis cell wall skeleton combined with trehalose dimycolate (P3). Cancer (in press, 1979)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Vosika, G., Schmidtke, J., Goldman, A. et al. Phase I–II study of intralesional immunotherapy with oil-attached Mycobacterium smegmatis cell wall skeleton and trehalose dimycolate. Cancer Immunol Immunother 6, 135–142 (1979). https://doi.org/10.1007/BF00205537
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00205537