Skip to main content
NCBI home page
Infection and Immunity logoLink to Infection and Immunity
. 1974 Nov;10(5):1044–1050. doi: 10.1128/iai.10.5.1044-1050.1974

Immunotherapy of Cancer with Nonliving BCG and Fractions Derived from Mycobacteria: Role of Cord Factor (Trehalose-6, 6′-Dimycolate) in Tumor Regression

A Bekierkunst 1,2,3, L Wang 1,2,3, R Toubiana 1,2,3, E Lederer 1,2,3
PMCID: PMC423059  PMID: 16558087

Abstract

Delipidated and deproteinized cell walls from Mycobacterium tuberculosis H37Ra suspended in 1.25% mineral oil emulsion cured established tumors in the skin and metastases in draining lymph nodes of guinea pigs (strain 2) after intratumoral administration in 33% of the cases examined. This was increased to 83% when a mixture of cord factor and the delipidated cell walls was used. A similarly high percentage of cures was obtained after administration of lyophilized, killed BCG alone or with addition of cord factor in 1% mineral oil emulsion. Lyophilized, killed BCG dispersed in a solution of tocopherol acetate in peanut oil or in peanut oil alone showed a limited tumor-regressive activity (36%). However, a mixture of BCG and cord factor suspended in the above media cured 80 and 69% of the treated animals, respectively.

Full text

PDF
1044

Images in this article

1046Image
on p.1046
1048Image
on p.1048

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Acharya P. V., Goldman D. S. Chemical composition of the cell wall of the H37Ra strain of Mycobacterium tuberculosis. J Bacteriol. 1970 Jun;102(3):733–739. doi: 10.1128/jb.102.3.733-739.1970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Adam A., Ciorbaru R., Petit J. F., Lederer E. Isolation and properties of a macromolecular, water-soluble, immuno-adjuvant fraction from the cell wall of Mycobacterium smegmatis. Proc Natl Acad Sci U S A. 1972 Apr;69(4):851–854. doi: 10.1073/pnas.69.4.851. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. BERLIN B. S. Gross physical properties of emulsified influenza virus vaccines and the adjuvant response. J Immunol. 1960 Jul;85:81–89. [PubMed] [Google Scholar]
  4. Bekierkunst A., Levij I. S., Yarkoni E. Suppression of urethan-induced lung adenomas in mice treated with trehalose-6,6-dimycolate (cord factor) and living bacillus Calmette Guérin. Science. 1971 Dec 17;174(4015):1240–1242. doi: 10.1126/science.174.4015.1240. [DOI] [PubMed] [Google Scholar]
  5. Bekierkunst A., Levij I. S., Yarkoni E., Vilkas E., Adam A., Lederer E. Granuloma formation induced in mice by chemically defined mycobacterial fractions. J Bacteriol. 1969 Oct;100(1):95–102. doi: 10.1128/jb.100.1.95-102.1969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bekierkunst A., Levij I. S., Yarkoni E., Vilkas E., Lederer E. Cellular reaction in the footpad and draining lymph nodes of mice induced by mycobacterial fractions and BCG bacilli. Infect Immun. 1971 Sep;4(3):245–255. doi: 10.1128/iai.4.3.245-255.1971. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bekierkunst A., Yarkoni E., Flechner I., Morecki S., Vilkas E., Lederer E. Immune response to sheep red blood cells in mice pretreated with mycobacterial fractions. Infect Immun. 1971 Sep;4(3):256–263. doi: 10.1128/iai.4.3.256-263.1971. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Bekierkunst A., Yarkoni E. Granulomatous hypersensitivity to trehalose-6,6'-dimycolate (cord factor) in mice infected with BCG. Infect Immun. 1973 Apr;7(4):631–638. doi: 10.1128/iai.7.4.631-638.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Esterly J. R., Sturner W. Q., Esterly N. B., Windhorst D. B. Disseminated BCG in twin boys with presumed chronic granulomatous disease of childhood. Pediatrics. 1971 Jul;48(1):141–144. [PubMed] [Google Scholar]
  10. FREUND J. The effect of paraffin oil and mycobacteria on antibody formation and sensitization; a review. Am J Clin Pathol. 1951 Jul;21(7):645–656. doi: 10.1093/ajcp/21.7.645. [DOI] [PubMed] [Google Scholar]
  11. FREUND J. The mode of action of immunologic adjuvants. Bibl Tuberc. 1956;(10):130–148. [PubMed] [Google Scholar]
  12. Hilleman M. R., Woodhour A. F., Friedman A., Phelps A. H. Studies for safety of adjuvant 65. Ann Allergy. 1972 Aug;30(8):477–483. [PubMed] [Google Scholar]
  13. Krementz E. T., Samuels M. S., Wallace J. H., Benes E. N. Clinical experiences in immunotherapy of cancer. Surg Gynecol Obstet. 1971 Aug;133(2):209–217. [PubMed] [Google Scholar]
  14. Lederer E. The mycobacterial cell wall. Pure Appl Chem. 1971;25(1):135–165. doi: 10.1351/pac197125010135. [DOI] [PubMed] [Google Scholar]
  15. Marks J., Jenkins P. A., Kilpatrick G. S., Engbaek H. C., Vergmann B. Pulmonary tuberculosis due to B.C.G. Br Med J. 1971 Jul 24;3(5768):229–230. doi: 10.1136/bmj.3.5768.229. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Mathé G., Amiel J. L., Schwarzenberg L., Schneider M., Cattan A., Schlumberger J. R., Hayat M., De Vassal F. Active immunotherapy for acute lymphoblastic leukaemia. Lancet. 1969 Apr 5;1(7597):697–699. doi: 10.1016/s0140-6736(69)92648-8. [DOI] [PubMed] [Google Scholar]
  17. Morton D., Eilber F. R., Malmgren R. A., Wood W. C. Immunological factors which influence response to immunotherapy in malignant melanoma. Surgery. 1970 Jul;68(1):158–164. [PubMed] [Google Scholar]
  18. NOLL H., BLOCH H., ASSELINEAU J., LEDERER E. The chemical structure of the cord factor of Mycobacterium tuberculosis. Biochim Biophys Acta. 1956 May;20(2):299–309. doi: 10.1016/0006-3002(56)90289-x. [DOI] [PubMed] [Google Scholar]
  19. Nathanson L. Regression of intradermal malignant melanoma after intralesional injection of Mycobacterium bovis strain BCG. Cancer Chemother Rep. 1972 Oct;56(5):659–665. [PubMed] [Google Scholar]
  20. Petit J. F., Adam A., Wietzerbin-Falszpan J., Lederer E., Ghuysen J. M. Chemical structure of the cell wall of Mycobacterium smegmatis. I. Isolation and partial characterization of the peptidoglycan. Biochem Biophys Res Commun. 1969 May 22;35(4):478–485. doi: 10.1016/0006-291x(69)90371-4. [DOI] [PubMed] [Google Scholar]
  21. Rapp H. J., Churchill W. H., Jr, Kronman B. S., Rolley R. T., Hammond W. G., Borsos T. Antigenicity of a new diethylnitrosamine-induced transplantable guinea pig hepatoma: pathology and formation of ascites variant. J Natl Cancer Inst. 1968 Jul;41(1):1–7. [PubMed] [Google Scholar]
  22. Seigler H. F., Shingleton W. W., Metzgar R. S., Buckley C. E., Bergoc P. M., Miller D. S., Fetter B. F., Phaup M. B. Non-specific and specific immunotherapy in patients with melanoma. Surgery. 1972 Jul;72(1):162–174. [PubMed] [Google Scholar]
  23. Sićević S. Generalized BCG tuberculosis with fatal course in two sisters. Acta Paediatr Scand. 1972 Mar;61(2):178–184. doi: 10.1111/j.1651-2227.1972.tb15922.x. [DOI] [PubMed] [Google Scholar]
  24. Sokal J. E., Aungst C. W. Response to BCG vaccination and survival in advanced Hodgkin's disease. Cancer. 1969 Jul;24(1):128–134. doi: 10.1002/1097-0142(196907)24:1<128::aid-cncr2820240117>3.0.co;2-c. [DOI] [PubMed] [Google Scholar]
  25. WOODHOUR A. F., JENSEN K. E., WARREN J. Development and application of new parenteral adjuvants. J Immunol. 1961 Jun;86:681–689. [PubMed] [Google Scholar]
  26. Watkins S. M. Unusual complication of B.C.G. vaccination. Br Med J. 1971 Feb 20;1(5746):442–442. doi: 10.1136/bmj.1.5746.442. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Yarkoni E., Wang L., Bekierkunst A. Suppression of growth of Ehrlich ascites tumor cells in mice by trehalose-6,6'-dimycolate (cord factor) and BCG. Infect Immun. 1974 Jun;9(6):977–984. doi: 10.1128/iai.9.6.977-984.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Zbar B., Bernstein I. D., Bartlett G. L., Hanna M. G., Jr, Rapp H. J. Immunotherapy of cancer: regression of intradermal tumors and prevention of growth of lymph node metastases after intralesional injection of living Mycobacterium bovis. J Natl Cancer Inst. 1972 Jul;49(1):119–130. [PubMed] [Google Scholar]
  29. Zbar B., Tanaka T. Immunotherapy of cancer: regression of tumors after intralesional injection of living Mycobacterium bovis. Science. 1971 Apr 16;172(3980):271–273. doi: 10.1126/science.172.3980.271. [DOI] [PubMed] [Google Scholar]
  30. Zbar B., Wepsic H. T., Rapp H. J., Whang-Peng J. Transplantable hepatomas induced in strain-2 guinea pigs by diethylnitrosamine: characterization by histology, growth, and chromosomes. J Natl Cancer Inst. 1969 Oct;43(4):821–831. [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES