Summary
A vaccine composed of BCG cell wall skeleton (CWS) and a trehalose dimycolate called P3, attached to microdroplets of mineral oil, was evaluated for activity and toxicity when injected into tumor nodules. A total of 99 nodules in 23 patients with metastatic melanoma and carcinoma of the breast were treated overa dose range of 150 μg, 300 μg, and 600 μg cell wall skeleton plus P3 per cm of nodule diameter. At least one injected nodule resolved in 11 of the 23 patients (48%), and 34% of all injected nodules resolved. Response correlated with nodule size of 1 cm or less, cutaneous location, and immunocompetence measured by PPD and recall skin testing. Toxicity became manifest in ulceration (61% of patients), fever (52%), and pain (26%).
Similar content being viewed by others
References
Adams, A., Ciorbaru, R., Petit, J., Lederer, E.: Isolation and properties of a macromolecular, water-soluble immuno-adjuvant fraction from the cell wall of Mycobacterium smegmatis. Proc. Natl. Acad. Sci. USA 69, 851–854 (1972)
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. 52, 95–101 (1974)
Bornstein, R. S., Mastrangelo, M. J., Sulit, H., Darwin, C., Yarbro, J. W., Prehn, L., Prehn, R. T.: Immunotherapy of melanoma with intralesional BCG. Natl. Cancer Inst. Monogr. 39, 213–220 (1973)
Chedid, L., Parant, M., Parant, F., Gustafson, R. H., Berger, F. M.: Biological study of a nontoxic, water-soluble, immunoadjuvant from mycobacterial cell walls. Proc. Natl. Acad. Sci. USA 69, 855–858 (1972)
Cuttner, J., Bekesi, J. G., Holland, J. F.: Chemoimmunotherapy of acute leukemia using MER. Proc. Am. Assoc. Cancer Res. 17, 196 (1976)
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 metastases from malignant melanoma. N. Engl. J. Med. 294, 237–240 (1976)
Gutterman, J. U., Mavligit, G., McBride, C., Frei, E. III, Freireich, E. J., Hersh, E. M.: Active immunotherapy with BCG for recurrent malignant melanoma. Lancet 1973 1, 1208–1212
Klein, E., Holtermann, O. A., Papermaster, B., Milgrom, H., Rosner, D., Kelin, L., Walker, K. J., Zbar, B.: Immunologic approaches to various types of cancer with the use of BCG and purified protein derivatives. Natl. Cancer Inst. Monogr. 39, 229–239 (1973)
Lieberman, R., Wybran, J., Epstein, W.: The immunologic and histopathologic changes of BCG-mediated tumor regression in patients with malignant melanoma. Cancer 35, 756–777 (1975)
McKneally, M. F., Maver, C., Kausel, H. W., Alley, R. D.: Regional immunotherapy with intrapleural BCG for lung cancer. J. Thorac. Cardiovasc. Surg. 72, 333–338 (1976)
Meyer, T. J., Ribi, E. E., Azuma, I., Zbar, B.: Biologically active components from mycobacterial cell walls. II. Suppression and regression of strain-2 guinea pig hepatoma. J. Natl. Cancer Inst. 52, 103–111 (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, 158–164 (1970)
Nathanson, L.: Regression of intradermal malignant melanoma after intralesional injection of mycobacterium bovis strain BCG. Cancer Chemother. Rep. 56, 659–665 (1972)
Pinsky, C. M., Hirshaut, Y., Oettgen, H. F.: Treatment of malignant melanoma by intratumoral injection of BCG. Natl. Cancer Inst. Monogr. 39, 225–228 (1973)
Ribi, E. E., Granger, D. L., Milner, K. C., et al.: Tumor regression caused by endotoxins and mycobacterial fractions. (Brief communication.) J. Natl. Cancer Inst. 55, 1253–1257 (1975)
Weiss, D. W., Stupp, Y., Many, N., Izak, G.: Treatment of acute myelocytic leukemia (AML) patients with MER tubercle bacillus fraction: A preliminary report. Transplant. Proc. 7 (Suppl.) 545–552 (1975)
Yamamura, Y., Yoshizake, K., Azuma, I., Yagura, T. S., Wanatabe, T.: Immunotherapy of human melanoma with cil-attached BCG cell wall skeleton. Gann 66, 355–363 (1975)
Yasumoto, K., Manabe, H., Ueno, M., Ohta, M., Ueda, H., Iida, A., Nomoto, K., Azuma, I., Yamamura, Y.: Immunotherapy of human lung cancer with BCG cell-wall skeleton. Gann 67, 787–795 (1976)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Richman, S.P., Gutterman, J.U., Hersh, E.M. et al. Phase I–II study of intratumor immunotherapy with BCG cell wall skeleton plus P3 . Cancer Immunol Immunother 5, 41–44 (1978). https://doi.org/10.1007/BF00199206
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00199206