Advertisement

Clinical Immunotherapeutics

, Volume 2, Issue 6, pp 409–414 | Cite as

Prospects for an Immunological Approach to Therapy of Ovarian Cancer

  • Grant D. MacLean
  • B. Michael Longenecker
Leading Article

Summary

Characterisation of changes in expression of carbohydrates and peptides on cancer mucins enables a reconsideration of immunotherapy of ovarian cancer. Natural immune responses to cancer mucins have been demonstrated. Some results with cell extracts have been encouraging, but there are inherent limitations to using such mixtures for immunotherapy. Successful animal model studies with synthetic vaccines have demonstrated that pretreatment with low dosage cyclophosphamide can be used to inhibit suppressor activity induced by natural cancer mucins.

Preliminary results from clinical trials with synthetic vaccines challenge us to redefine ‘successful’ cancer therapy. Combination biomodulation strategies may become the therapy of the future for ovarian cancer.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Scott OCA. Tumor transplantation and tumor immunity: a personal view. Cancer Res 1991; 51: 757–63PubMedGoogle Scholar
  2. 2.
    Hakomori S. Aberrant glycosylation in cancer cell membranes as focused on glycolipids: overview and perspectives. Cancer Res 1985; 45: 2405–14PubMedGoogle Scholar
  3. 3.
    Longenecker BM, MacLean GD. Prospects for mucin epitopes in cancer vaccines. Immunologist 1993; 1: 89–93Google Scholar
  4. 4.
    Longenecker BM, Willans DJ, MacLean GD, et al. Monoclonal antibodies and synthetic tumor-associated glycoconjugates in the study of the expression of Thomsen-Friedenreich-like and Tn-like antigens on human cancers. J Natl Cancer Inst 1987; 78(3): 489–96PubMedGoogle Scholar
  5. 5.
    Springer GF. T and Tn, general carcinoma autoantigens. Science 1984; 224(4654): 1198–206PubMedCrossRefGoogle Scholar
  6. 6.
    MacLean GD, Longenecker BM. Clinical significance of the Thomsen-Friedenreich antigen. Cancer Biol 1991; 2: 433–9Google Scholar
  7. 7.
    Ghazizadeh M, Oguro T, Sasaki Y, et al. Immunohistochemical and ultrastructural localization of T antigen in ovarian tumors. Am J Clin Pathol 1990; 93(3): 315–21PubMedGoogle Scholar
  8. 8.
    Itzkowitz SH, Yuan M, Montgomery CK, et al. Expression of Tn, sialosyl-Tn, and T antigens in human colon cancer. Cancer Res 1989; 49: 197–204PubMedGoogle Scholar
  9. 9.
    Itzkowitz SH, Bloom EJ, Kokal WA, et al. Sialosyl-Tn, a novel mucin antigen associated with prognosis in colorectal cancer patients. Cancer 1990; 66(9): 1960–6PubMedCrossRefGoogle Scholar
  10. 10.
    Kobayashi H, Terao T, Kawashima Y. Serum sialyl-Tn as an independent predictor of poor prognosis in patients with epithelial ovarian cancer. J Clin Oncol 1992; 10(1): 95–101PubMedGoogle Scholar
  11. 11.
    Gendler S, Taylor-Papadimitriou J, Duhig T, et al. A highly immunogenic region of a human polymorphic epithelial mucin expressed by carcinomas is made up of tandem repeats. J Biol Chem 1988; 263: 12820–3PubMedGoogle Scholar
  12. 12.
    Onsrud M. Immunosuppressive effects of peritoneal fluids from ovarian cancer patients. Gynecol Oncol 1986; 23: 316–22PubMedCrossRefGoogle Scholar
  13. 13.
    Fung PYS, Longenecker BM. Specific immunosuppressive activity of epiglycanin, a mucin-like glycoprotein secreted by a murine mammary adenocarcinoma (TA3-HA). Cancer Res 1991; 51: 1170–6PubMedGoogle Scholar
  14. 14.
    Berd D, Mastrangelo MJ, Engstrom PF, et al. Augmentation of the human immune response by cyclophosphamide. Cancer Res 1982; 42: 4862–6PubMedGoogle Scholar
  15. 15.
    Berd D, Maguire Jr HC, Mastrangelo MJ. Potentiation of human cell-mediated and humoral immunity by low-dose cyclophosphamide. Cancer Res 1984; 44: 5439–43PubMedGoogle Scholar
  16. 16.
    Mastrangelo MJ, Berd D, Maguire Jr HC. The immunoaugmenting effects of cancer chemotherapeutic agents. Semin Oncol 1986; 13(2): 186–94PubMedGoogle Scholar
  17. 17.
    Berd D, Mastrangelo MJ. Effect of low dose cyclophosphamide on the immune system of cancer patients: depletion of CD4+, 2H4+ suppressor-inducer T-cells. Cancer Res 1988; 48: 1671–5PubMedGoogle Scholar
  18. 18.
    Hoover SK, Barrett SK, Turk TMT, et al. Cyclophosphamide and abrogation of tumor-induced suppressor T cell activity. Cancer Immunol Immunother 1990; 31: 121–7PubMedCrossRefGoogle Scholar
  19. 19.
    Silverstein AM. The concept of immunological specificity. A history of immunology. San Diego: Academic Press, 1989: 305–10Google Scholar
  20. 20.
    Mitchell MS. Biomodulators in cancer treatment. J Clin Pharmacol 1992; 32: 2–9PubMedGoogle Scholar
  21. 21.
    Klug TL, Bast Jr RC, Niloff JM, et al. Monoclonal antibody immunoradiometric assay for an antigenic determinant (CA 125) associated with human epithelial ovarian carcinomas. Cancer Res 1984; 44: 1048–53PubMedGoogle Scholar
  22. 22.
    Niloff JM, Knapp RC, Lavin PT, et al. The CA 125 assay as a predictor of clinical recurrence in epithelial ovarian cancer. Am J Obstet Gynecol 1986; 155(1): 56–60PubMedGoogle Scholar
  23. 23.
    Patsner B, Day Jr TG. Predictive Value of CA 125 levels in advanced ovarian cancer. Am J Obstet Gynecol 1987; 156(2): 440–1PubMedGoogle Scholar
  24. 24.
    Capstick V, MacLean GD, Suresh MR, et al. Clinical evaluation of a new two-site assay for CA 125 antigen. Int J Biol Markers 1991; 6(2): 129–35PubMedGoogle Scholar
  25. 25.
    MacLean GD, McEwan AJB, Noujaim AA, et al. Two novel monoclonal antibodies have potential for gynecologic cancer imaging. Antibody Immunoconjug Radiopharm 1991; 4(3): 297–308Google Scholar
  26. 26.
    McEwan AJB, MacLean GD, Hooper HR, et al. MAb 170H.82: an evaluation of a novel panadenocarcinoma monoclonal antibody labelled with 99Tc m and with 111In. Nucl Med Commun 1992; 13: 11–9PubMedCrossRefGoogle Scholar
  27. 27.
    Colcher D, Esteban J, Carrasquillo JA, et al. Complementation of intracavitary and intravenous administration of a monoclonal antibody (B72.3) in patients with carcinoma. Cancer Res 1987; 47: 4218–24PubMedGoogle Scholar
  28. 28.
    Rosenblum MG, Kavanagh JJ, Burke TW, et al. Clinical pharmacology, metabolism, and tissue distribution of 90Y-labeled monoclonal antibody B72.3 after intraperitoneal administration. J Natl Cancer Inst 1991; 83(22): 1629–36PubMedCrossRefGoogle Scholar
  29. 29.
    Baum RP, Noujaim AA, Nanci A, et al. Clinical course of ovarian cancer patients under repeated stimulation of HAMA using MAb OC125 and B43.13. Hybridoma 1993; 12(5): 583–9PubMedCrossRefGoogle Scholar
  30. 30.
    Bast Jr RC, Knapp RC. Immunologic approaches to the management of ovarian carcinoma. Semin Oncol 1984; 11(3): 264–74PubMedGoogle Scholar
  31. 31.
    Ferrini S, Biassoni R, Moretta A, et al. Clonal analysis of T lymphocytes isolated from ovarian carcinoma ascitic fluid: phenotypic and functional characterization of T-cell clones capable of lysing autologous carcinoma cells. Int J Cancer 1985; 36: 337–43PubMedGoogle Scholar
  32. 32.
    Freedman RS, Edwards CL, Bowen JM, et al. Viral oncolysates in patients with advanced ovarian cancer. Gynecol Oncol 1988; 29: 337–47PubMedCrossRefGoogle Scholar
  33. 33.
    Ioannides CG, Platsoucas CD, O’Brian CA. Viral oncolysates in cancer treatment: immunological mechanisms of action. Anticancer Res 1989; 9: 535–44PubMedGoogle Scholar
  34. 34.
    MacLean GD, Reddish MA, Bowen-Yacyshyn MB, et al. Active specific immunotherapy against adenocarcinomas. Cancer Invest 1994; 12(1): 46–56PubMedCrossRefGoogle Scholar
  35. 35.
    Springer GF, Parimal RD, Tegtmeyer H, et al. T/Tn antigen vaccine is effective and safe in preventing recurrence of advanced human breast carcinoma. Cancer Biother 1994; 9(1): 1–17CrossRefGoogle Scholar
  36. 36.
    Ioannides CG, Fisk B, Jerome KR, et al. Cytotoxic T cells from ovarian malignant tumors can recognize polymorphic epithelial mucin core peptides. J Immunol 1993; 151(7): 3693–703PubMedGoogle Scholar
  37. 37.
    Fung PYS, Madej M, Koganty RR, et al. Active specific immunotherapy of a murine mammary adenocarcinoma using a synthetic tumor-associated glycoconjugate. Cancer Res 1990; 50: 4308–14PubMedGoogle Scholar
  38. 38.
    MacLean GD, Bowen-Yacyshyn MB, Samuel J, et al. Active immunization of human ovarian cancer patients against a common carcinoma (Thomsen-Friedenreich) determinant using a synthetic carbohydrate antigen. J Immunother 1992; 11: 292–305PubMedCrossRefGoogle Scholar
  39. 39.
    MacLean GD, Reddish MA, Koganty RR, et al. Immunization of breast cancer patients using a synthetic sialyl-Tn glycoconjugate plus Detox adjuvant. Cancer Immunol Immunother 1993; 36: 215–22PubMedCrossRefGoogle Scholar
  40. 40.
    Hanna MG, Key ME. Immunotherapy of metastases enhances subsequent chemotherapy. Science 217: 367–9Google Scholar
  41. 41.
    Kleinerman ES, Howser D, Young RC, et al. Defective monocyte killing in patients with malignancies and restoration of function during chemotherapy. Lancet 1980; 1102–5Google Scholar
  42. 42.
    Collins JL, Kao MS. The anticancer drug, cisplatin, increases the naturally occurring cell-mediated lysis of tumor cells. Cancer Immunol Immunother 1989; 29: 17–22PubMedCrossRefGoogle Scholar
  43. 43.
    Nanbara S, Arinaga S, Akiyoshi T. Augmentation of the generation of lymphokine-activated killer cells after a single dose of mitomycin C in cancer patients. Cancer Immunol Immunother 1989; 29: 237–41PubMedCrossRefGoogle Scholar
  44. 44.
    Oldham RK. Cancer and diabetes: are these similarities? Mol Biother 1990; 2: 130–1PubMedGoogle Scholar
  45. 45.
    Schipper H, Goh CR, Wang TL. Rethinking cancer: should we control rather than kill? Part 1. Can J Oncol 1993; 3(3): 207–16Google Scholar
  46. 46.
    Schipper H, Goh CR, Wang TL. Rethinking cancer: should we control rather than kill? Part 2. Can J Oncol 1993; 3(4): 220–4Google Scholar

Copyright information

© Adis International Limited 1994

Authors and Affiliations

  • Grant D. MacLean
    • 1
    • 2
  • B. Michael Longenecker
    • 3
    • 4
  1. 1.Department of Oncology, Faculty of MedicineUniversity of AlbertaEdmontonCanada
  2. 2.Cross Cancer InstituteEdmontonCanada
  3. 3.Department of Immunology, Faculty of MedicineUniversity of AlbertaEdmontonCanada
  4. 4.Biomira Inc.EdmontonCanada

Personalised recommendations