Summary
A heptavalent lipopolysaccharide vaccine of Pseudomonas aeruginosa (Pseudogen) was administered at four dose levels (0.1, 0.25, 0.5, and 0.75 mg/m2) to patients with advanced metastatic cancer that had proved refractory to chemotherapy. The vaccine was administered subcutaneously twice weekly. Local toxicity was seen in erythema, edema, pain and tenderness at the site of injection, and painful regional lymphadenopathy; manifestations of systemic toxicity included fever, chills, myalgias, nausea, and vomiting. Toxicity showed a clear-cut dose dependence. The maximally tolerated dose by this route and schedule was 0.5 mg/m2. A significant rise of antibody titers was observed at all four dose levels. Evaluation of the delayed cutaneous hypersensitivity response to recall antigens and to the pseudomonas vaccine, and quantification of peripheral blood T and B cell levels and of in vitro lymphocyte blastogenic responses to commonly used mitogens and pseudomonas vaccine failed to demonstrate significant change from pretreatment values. Clinical trials to evaluate the therapeutic efficacy of pseudomonas vaccine with or without chemotherapy can be undertaken safely with this route and schedule.
Similar content being viewed by others
References
Adkins, E., Frances, L.: Role of lymphocytes in the pyrogenic response: comparison of endotoxin with specific antigen and the non-specific mitogen, Con-Conavalin-A. I. infect. Dis. 128 (Suppl.), S277-S283 (1973)
Alexander, J. W., Fischer, M. W.: Immunological control of Pseudomonas infection in burn patients: A clinical evaluation. Arch. Surg. 102, 31–35 (1971)
Alexander, J. W., Fischer, M. W.: Immunization against Pseudomonas in infection after thermal injury. I. infect. Dis. 130, S152-S158 (1974)
Alexander, J. W., Fischer, M. W., McMillan, B. G., Altemeier, W. A.: Prevention of invasive Pseudomonas infection in burns with a new vaccine. Arch. Surg. 99, 249–256 (1969)
Bober, L. A., Kranepool, M. J., Hollander, V. P.: Inhibitory effect of endotoxin on the growth of plasma cell tumor. Cancer Res. 36, 927–929 (1976)
Bradley, S. G., Adams, A. C., Smith, M. C.: Potentiation of the toxicity of Mithramycin by bacterial lipopolysaccharide. Antimicrob. Agents Chemother. 7, 322–327 (1975)
Carswell, E. A., Old, L. J., Kassel, R. L., Green, S., Fiore, N., Williamson, B.: An endotoxin-induced serum factor that causes necrosis of tumors. Proc. nat. Acad. Sci. (Wash.) 72, 3666–3670 (1975)
Clarkson, B. D., Dowling, M. D., Gee, T. S., Cunningham, I. B., Burchenal, A. H.: Treatment of acute leukemia in adults. Cancer 36, 775–795 (1975)
Coley, W. B.: A report of recent cases of inoperable sarcomas successfully treated with mixed toxins of Erysipelas and Bacillus Prodigiosus. Surg. Gynec. Obstet. 13, 174–190 (1911)
Creech, H. J., Hamilton, M. A., Diller, I. C.: Comparative studies of the immunological, toxic and tumor necrotizing properties of polysaccharides from Serratia Marcescens cells. Canad. J. Biochem. 42, 593–603 (1964)
Diller, I. C. Degenerative changes induced in tumor cells by serratia Marcescens polysaccharide. Cancer Res. 7, 605–626 (1947)
Feller, I., Pierson, C.: Pseudomonas vaccine and hyperimmune plasma for burned patients. Arch. Surg. 97, 275–279 (1968)
Gee, T. S., Clarkson, B. D.: Pseudomonas Aeruginosa vaccine in a treatment protocol for adult patients with acute non-lymphoblastic leukemia: A preliminary report. In: Immunotherapy of cancer: Present status of trials in man (ed. W. D. Terry). New York: Raven Press (in press, 1978)
Gordon, W. C., Mandy, W. J., Prager, M. D.: Differential effect of Asparaginase of lymphocytes of populations and alleviation of the immunosuppression by Lipopolysaccharide. Cancer Immunol. Immunother. 1, 205–209 (1976)
Green, S., Carswell, E., Old, L. J., Fiore, N., Dobriansky, A., Mamaril, F., Schwartz, M. K.: Mechanisms of endotoxin-induced tumor hemorrhagic necrosis. Proc. Amer. Ass. Cancer Res. 15, 139 (1974)
Gutterman, J. U., Mavligit, G. N., Hersh, E. M.: Chemoimmunotherapy of human solid tumors. Med. Clin. N. Amer. 60, 411–461 (1976)
Haghbin, M., Armstrong, D., Murphy, M. L.: Controlled prospective trial of Pseudomonas Aeruginosa vaccine in children with acute leukemia. Cancer 32, 761–770 (1973)
Hanessian, S., Regan, W., Watson, D., Haskell, T. H.: Isolation and characterization of antigenic components of a new heptavalent pseudomonas vaccine. Nature (Lond.) New Biol. 229, 209–210 (1971)
Hartwell, J. L., Shear, M. J., Adams, R. J., Jr.: Chemical treatment of tumors. VII: Nature of hemorrhage-producing fraction from Serratia Marcescens (Bacillus Prodigiosus) culture filtrates. J. nat. Cancer Inst. 4, 107–122 (1943)
Havas, H. F., Donnelly, A. J.: Mixed bacterial toxins in the treatment of tumors. IV. Response of methylcholanthrene induced spontaneous and transplanted tumors in mice. Cancer Res. 21, 17–25 (1961)
Hersh, E. M., Gutterman, J. U., Mavligit, G., McCredie, K. B., Burgess, M. A., Mathews, A., Freireich, E. J.: Serial studies of immunocompetence of patients undergoing chemotherapy for acute leukemia. J. clin. Invest. 54, 401–408 (1974)
Horn, R. G.: Evidence for participation of granulocytes in the pathogenesis of degeneralized Schwartzman reaction: a review. J. infect. Dis. 128 (Suppl.), S134-S143 (1973)
Ikawa, M., Koepfli, J. B., Mudd, L. G., Niemann, C.: An agent from E. coli causing hemorrhage and regression of the experimental mouse tumor. I: Isolation and properties. J. nat. Cancer Inst. 13, 157–166 (1952)
Lamoureux, G., Turcotte, R., Portelance, Z.: BCG in cancer immunotherapy. New York: Grune and Stratton 1976
Landy, M., Pillemer, L.: Increased resistance to infection and accompanying alteration in properdin levels following administration of bacterial lipopolysaccharides. J. exp. Med. 104, 383–388 (1956)
Marecki, N. M., Bradley, S. G.: Enhanced toxicity for mice of combinations of bacterial endotoxin with antitumor drugs. Antimicrob. Agents Chemother. 3, 599–606 (1973)
Miller, T. R., Nicholson, J. T.: End results in reticulum cell sarcoma of bone treated by bacterial toxin therapy alone or combined with surgery and/or radiotherapy (47 cases) or concurrent infection (5 cases). Cancer 27, 524–547 (1971)
Morton, D. L.: Cancer immunotherapy: An overview. Semin. Oncol. 1, 297–310 (1974)
Nauts, H. C.: Beneficial effects of immunotherapy (bacterial toxins) on sarcoma of the soft tissues, other than lymphosarcoma. New York: Cancer Research Institute, Inc. 1975
Parr, I., Wheeler, E., Alexander, P.: Similarities of the antitumor actions of endotoxin, lipid A and double stranded RNA. Brit. J. Cancer 27, 370–389 (1973)
Peavy, D. L., Shanes, J. W., Adler, W. H., Smith, R. T.: Selective effects of bacterial endotoxins on various sub-populations of lymphoreticular cells. J. infect. Dis. 128 (Suppl.), S91-S99 (1973)
Pennington, J. E., Renault, H. Y., Wood, R. E., Robinson, R. A., Levine, A. S.: Use of a Pseudomonas Aeruginosa vaccine in patients with acute leukemia and cystic fibrosis. Amer. J. Med. 58, 629–636 (1975)
Pilch, J. H., Myers, G. H., Sparks, F. C., Golub, S. H.: Prospect for the immunotherapy of cancer. Curr. Probl. Surg. 1975
Polk, H. C., Jr., Bordan, B. S., Aldrete, J. A.: Prevention of Pseudomonas respiratory infection in a surgical intensive care unit. Ann. Surg. 177, 607–615 (1973)
Ribi, E. E., Granger, D. L., Millner, K. C., Strain, S. M.: Brief communication: tumor regression caused by endotoxins and mycobacterial fractions. J. nat. Cancer Inst. 55, 1253–1257 (1975)
Rowley, D.: Rapidly induced changes in the level of non-specific immunity in laboratory animals. Griffith's J. exp. Path. 37, 223–234 (1956)
Shear, M. J., Perrault, A.: Chemical treatment of tumors IX: Reaction of mice with primary subcutaneous tumors to injection of the hemorrhage-producing bacteria Polysaccharide. J. nat. Cancer Inst. 4, 461–476 (1944)
Shear, M. J., Turner, F. C.: Chemical treatment of tumors. V: Isolation of hemorrhage-producing fraction from Serratia Marcescens (Bacillus Prodigiosus) culture filtrates. J. nat. Cancer Inst. 4, 81–97 (1943)
Smith, W. W., Alderman, I. M., Gillespie, R. E.: Hematopoietic recovery induced by bacterial endotoxin in irradiated mice. Amer. J. Physiol. 192, 549–556 (1958)
Strausser, H. R., Bober, L. A.: Inhibition of tumor growth and survival of aged mice inoculated with Maloney tumor transplants and treated with endotoxin. Cancer Res. 32, 2156–2159 (1972)
Whitby, J. L., Rolley, D.: The role of macrophages in the elimination of bacteria from the mouse peritoneum. Brit. J. exp. Path. 40, 358–370 (1959)
Young, L. S., Meyer, R. D., Armstrong, D.: Pseudomonas Aeruginosa vaccine in cancer patients. Ann. intern. Med. 79, 518–527 (1973)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Hortobagyi, G.N., Gutterman, J.U., Snyder, R.D. et al. Pseudomonas vaccine: A phase I evaluation for cancer research. Cancer Immunol Immunother 4, 201–207 (1978). https://doi.org/10.1007/BF00204741
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00204741