Advertisement

Medical Oncology and Tumor Pharmacotherapy

, Volume 3, Issue 3–4, pp 147–152 | Cite as

Immunotoxin therapy of malignant melanoma

  • Lynn E. Spitler
Immunoglobulins
  • 15 Downloads

Abstract

Current standard therapies for metastatic malignant melanoma are poor, and surgical excision of disease remains the cornerstone of melanoma management. Unmodified monoclonal antibodies have been used therapeutically in this, and other, malignancies, but results have been disappointing. This has led to attempts to improve the efficacy of monoclonal antibodies by using them to target therapeutic modalities to tumors. These therapeutic modalities include chemotherapeutic, radiotherapeutic and cytotoxic agents. An example of the latter is ricin A-chain, which is so potent that it has been reported that one molecule of it entering the cytosol is sufficient to cause cell death. Preclinical studies support the potential of immunotoxins as effective therapy for malignancy. A phase I–II trial of immunotoxin therapy of malignant melanoma has been completed and a trial to determine clinical efficacy has been implemented.

Key words

Immunotoxin Melanoma Monoclonal antibodies Immunotherapy 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Silverberg E: Cancer statistics.Cancer 34, 6 (1984).Google Scholar
  2. 2.
    Jensen O M, Bolander A M: Trends in malignant melanoma of the skin.World Health Statistics Quarterly 33, 2 (1980).Google Scholar
  3. 3.
    Silverberg E: Cancer in young adults (ages 15 to 34).Cancer 33, 32 (1982).Google Scholar
  4. 4.
    Moseley H S, Eilber F R, Morton D L: Melanoma, in Haskell C M (ed):Cancer Treatment, pp. 678–694. Philadelphia, W. B. Saunders (1980).Google Scholar
  5. 5.
    Luce J K: Chemotherapy of melanoma.Seminars in Oncology 2, 179 (1975).PubMedGoogle Scholar
  6. 6.
    Seigler H F, Lucas V S, Pickett N J, Huang A T: DTIC, CCNU, bleomycin and vincristine (BOLD) in metastatic melanoma.Cancer 46, 2346 (1980).PubMedCrossRefGoogle Scholar
  7. 7.
    Nathanson L, Kaufman S D, Carey R W: Vinblastine, infusion, bleomycin andcis-dichlorodiammine-platinum chemotherapy in metastatic melanoma.Cancer 48, 1290 (1981).PubMedCrossRefGoogle Scholar
  8. 8.
    Hill G J, Moss S E, Golomb F M, Grage T B, Fletcher W S, Minton J P, Krementz E T: DTIC and combination therapy for melanoma: II DTIC (NSC 45388) Surgical Adjuvant Study Co (7) Protocol 7040.Cancer 47, 2556 (1981).PubMedCrossRefGoogle Scholar
  9. 9.
    Balch C, Murray D, Presant G, Bartolucci A A: Ineffectiveness of adjuvant chemotherapy using DTIC and cyclophosphamide in patients with resectable metastatic melanoma.Surgery II, 454 (1984).Google Scholar
  10. 10.
    Pinsky C M, Hirshaut Y, Wanebo H J, Fortner J G, Mike V, Schottenfeld D, Oettgen H F: Randomized trial of bacillus Calmet-Guérin (percutaneous administration) as surgical adjuvant immunotherapy for patients with Stage II melanoma.Ann NY Acad Sci 277, 187 (1976).PubMedCrossRefGoogle Scholar
  11. 11.
    Cunningham T J, Schoenfeld D, Nathanson L, Wolter J, Patterson W B, Cohen M H: A controlled study of adjuvant therapy in patients with stage I and II malignant melanoma, in Terry W D, Windhorst D (eds):Immunotherapy of Cancer: Present Status of Trials in Man, pp. 19–26. New York, Raven Press (1978).Google Scholar
  12. 12.
    Morton D L, Holmes E C, Eilber F R, Sparks F C, Ramming K P: Adjuvant immunotherapy of malignant melanoma: preliminary results of a randomized trial in patients with lymph node metastases, in Terry W D, Windhorst D (eds):Immunotherapy of Cancer: Present Status of Trials in Man, pp. 57–64. New York, Raven Press (1978).Google Scholar
  13. 13.
    Spitler L E, Sagebiel R: A randomized trial of levamisole versus placebo as adjuvant therapy in malignant melanoma.New Engl J Med 303, 1143 (1980).PubMedGoogle Scholar
  14. 14.
    Bukowski R M, Deodhar S, Hewlett J S, Greenstreet R: Randomized controlled trial of transfer factor in stage II malignant melanoma.Cancer 51, 269 (1983).PubMedCrossRefGoogle Scholar
  15. 15.
    Hilaris B S, Rabin M, Calabrese A S, Phillips R F, Herschkeuk U K: Value of radiation therapy for distant metastasis for malignant melanoma.Cancer 16, 765 (1963).PubMedCrossRefGoogle Scholar
  16. 16.
    Gottlieb J A, Frei E, Luce J K: An evaluation of the management of patients with cerebral metastases from malignant melanoma.Cancer 29, 701 (1972).PubMedCrossRefGoogle Scholar
  17. 17.
    Feun L G, Burgess M A, Hersh E M, Benjamin R S, Gehan E A, Murphy W K: The natural history of Stage IV-A melanoma.Proc Am Ass Cancer Res/Am Soc Clin Oncol (ASCO abstract)22, C372 (1981).Google Scholar
  18. 18.
    Nadler L M, Stashenko P, Hardy R, Kaplan W D, Button L M, Kufe D W, Antman K H, Schlossman S F: Serotherapy of a patient with a monoclonal antibody directed against a human lymphoma associated antigen.Cancer Res 40, 3147 (1980).PubMedGoogle Scholar
  19. 19.
    Miller R A, Oseroff A R, Stratte P T, Levy R: Monoclonal antibody therapeutic trials in seven patients with T-cell lymphoma.Blood 62, 988 (1983).PubMedGoogle Scholar
  20. 20.
    Miller R A, Maloney D G, Warnke R, Levy R: Treatment of B cell lymphoma with monoclonal anti-idiotype antibody.New Engl J Med 306, 517 (1982).PubMedGoogle Scholar
  21. 21.
    Ritz J, Pesando J M, Sallan S E, Clavell L A, Notis-McConarty J, Rosenthal P, Schlossman S F: Serotherapy of acute lymphoblastic leukemia with monoclonal antibody.Blood 58, 141 (1981).PubMedGoogle Scholar
  22. 22.
    Dillman R O, Shawler D L, Sobol R E, Collins H A, Beauregard J C, Wormsley S B, Royston I: Murine monoclonal antibody therapy in two patients with chronic lymphocytic leukemia.Blood 59, 1036 (1982).PubMedGoogle Scholar
  23. 23.
    Sears H F, Mattis J, Herlyn D, Hayry P, Atkinson B, Ernst C, Steplewski Z, Koprowski H: Phase I clinical trial of monoclonal antibody in treatment of gastro-intestinal tumours.Lancet i, 762 (1982).CrossRefGoogle Scholar
  24. 24.
    Lemkin S, Tokita K, Sherman G, Simko T, Schwartz L, Ciccirilli J, Drew S, Terasaki P: Phase I–II study of monoclonal antibodies in gastrointestinal cancer.ASCO Abstracts, C181 (1984).Google Scholar
  25. 25.
    Remlinger K, Martin P J, Harper J A, Doney D C, Smith A, Deeg H J, Sullivan K, Storb R, Thomas E D: Murine monoclonal anti-T cell antibodies for treatment of steroid-resistant acute graft-versus-host disease.Hum Immun 9, 21 (1984).PubMedCrossRefGoogle Scholar
  26. 26.
    Cosimi A B, Colvin R B, Burton R C, Rubin R H, Goldstein G, Kung P C, Hansen W P, Delmonico F L, Russell P S: Use of monoclonal antibodies to T-cell subsets for immunologic monitoring and treatment in recipients of renal allografts.New Engl J Med 305, 308 (1981).PubMedGoogle Scholar
  27. 27.
    Oldham R, Woodhouse C, Schroff R, Abrams P, Fer M, Kimball E, Foon K, Morgan A C: Monoclonal antibody therapy of malignant melanoma:in vivo localization in cutaneous metastasis after intravenous administration.ASCO Abstracts, C251 (1984).Google Scholar
  28. 28.
    Sobol R E, Dillman R O, Smith J D, Imai K, Ferrone S, Shawler D, Glassy M, Royston I: Phase I evaluation of murine monoclonal antimelanoma antibody in man: preliminary observations, in Mitchell M S, Oettgen H F (eds):Hybridomas in Cancer Diagnosis and Treatment, New York, Raven Press (1982).Google Scholar
  29. 29.
    Goodman G E, Baumier P, Hellstrom I, Hellstrom K E: Phase I trial of two murine monoclonal antibodies in human melanoma.ASCO Abstracts, C262 (1984).Google Scholar
  30. 30.
    Larson S M, Carrasquillo J A, Krohn KA, Brown J P, McGuffin R W, Ferens J M, Graham M M, Hill L D, Beaumier P L, Hellström K E, Hellström I: Localization of131I-labeled p97-specific Fab fragments in human melanoma as a basis for radiotherapy.J Clin Invest 72, 2101 (1983).PubMedCrossRefGoogle Scholar
  31. 31.
    Houghton A N, Mintzer D, Cordon-Cardo C, Welt S, Fliegel B, Vadhan S, Carswell E, Melamed M R, Oettgan H F, Old L J: Mouse monoclonal IgG3 antibody detecting GD3 ganglioside: a phase I trial in patients with malignant melanoma.Proc Natl Acad Sci, USA 82, 1242 (1985).PubMedCrossRefGoogle Scholar
  32. 32.
    Ritz J, Schlossman S F: Utilization of monoclonal antibodies in the treatment of leukemia and lymphoma.Blood 59, 1 (1982).PubMedGoogle Scholar
  33. 33.
    Rudiger H: Lectins, an introduction, in Bog-Hansen T C (ed):Lectins: Biology, Biochemistry, Clinical Biochemistry, Vol. 1. New York, Walter de Gruyter (1981).Google Scholar
  34. 34.
    Franz H, Ziska P: Affinitins: combining sites containing proteins, in Bog-Hansen TC (ed):Lectins: Biology, Biochemistry, Clinical Biochemistry, Vol. 1. New York, Walter de Gruyter (1981).Google Scholar
  35. 35.
    Olsnes S, Pihl A: Toxic lectins and related proteins, in Cohen P and Van Heynigen S (eds):Molecular Action of Toxins and Viruses. Amsterdam, Elsevier Biomedical Press (1982).Google Scholar
  36. 36.
    Fodstad O, Johannessen J V, Schjerven L, Pihl A: Toxicity of abrin and ricin in mice and dogs.J Toxic Envir Hlth 5, 1073 (1977).CrossRefGoogle Scholar
  37. 37.
    Vitetta E S, Krolick K A, Miyama-Inaba M, Cushley W, Uhr J W: Immunotoxins: a new approach to cancer therapy.Science 219, 644 (1983).PubMedCrossRefGoogle Scholar
  38. 38.
    Lin J Y, Tserna K Y, Chan C C, Lin L T, Tung T C: Abrin and ricin: new antitumor substances.Nature 227, 292 (1970).PubMedCrossRefGoogle Scholar
  39. 39.
    Tung T C, Hsu C T, Lin J W: Therepeutic effect of abrin and ricin on human cancers.J Formosan Med Ass 70, 41 (1971).Google Scholar
  40. 40.
    Fodstad O, Olsnes S, Pihl A: Inhibitory effect of abrin, ricin on the growth of transplantable murine tumors and of abrin on human cancers in nude mice.Cancer Res 37, 4559 (1977).PubMedGoogle Scholar
  41. 41.
    Fodstad O, Kvalheim G, Godal A, Lotsberg J, Aamdal S, Host H, Pihl A: Phase I study of the plant protein ricin.Cancer Res 44, 862 (1984).PubMedGoogle Scholar
  42. 42.
    Fodstad O, Pilh A: Synergistic effect of ricin in combination with daunorubicin,cis-dichlorodiammine-platinum(II) and vincristine in systemic L1210 leukemia.Cancer Res 42, 2152 (1982).PubMedGoogle Scholar
  43. 43.
    Gilliland D G, Steplewski Z, Collier R J, Mitchell K F, Chang T H, Koprowski H: Antibody directed cytotoxic agents: use of monoclonal antibody to direct the action of toxin A chains to colorectal carcinoma cells.Proc Natl Acad Sci, USA 77, 4539 (1980).PubMedCrossRefGoogle Scholar
  44. 44.
    Trowbridge I S, Domingo D L: Anti-transferrin receptor monoclonal antibody and toxin-antibody conjugates affect growth of human tumor cells.Nature (Lond) 294, 171 (1981).CrossRefGoogle Scholar
  45. 45.
    Seon B K: Specific killing of human T leukemia cell by immunotoxins prepared with ricin A chain and monoclonal antihuman T-cell leukemia antibodies.Cancer Res 44, 259 (1984).PubMedGoogle Scholar
  46. 46.
    Krolick K A, Villemez C, Isakson P, Uhr J W, Vitetta E S: Selective killing of normal or neoplastic B cells by antibodies coupled to the A chain of ricin.Proc Natl Acad Sci, USA 77, 5419 (1980).PubMedCrossRefGoogle Scholar
  47. 47.
    Krolick K A, Yuan D, Vitetta E S: Specific killing of a human breast carcinoma cell line by a monoclonal antibody to the A chain of ricin.J Immun Immunother 12, 39 (1981).Google Scholar
  48. 48.
    Blythman H E, Casellas P, Gros O, Gros P, Jansen F K, Paolucci F, Pau B, Vidal H: Immunotoxins: hybrid molecules of monoclonal antibodies and toxin subunit specifically kill tumor cells.Nature 290, 145 (1981).PubMedCrossRefGoogle Scholar
  49. 49.
    Youle R J, Neville D M Jr: Kinetics of protein synthesis inactivation by ricin A anti-thy 1.1 monoclonal antibody hybrids.J Biol Chem 257, 1598 (1982).PubMedGoogle Scholar
  50. 50.
    Raso V, Ritz J, Basola M, Schlossman S F: Monoclonal antibody-ricin A chain conjugate selectively cytotoxic for cells bearing the common acute lymphoblastic leukemia antigen.Cancer Res 42, 457 (1982).PubMedGoogle Scholar
  51. 51.
    Ramakrishnan S, Houston L L: Prevention of growth of leukemia cells in mice by monoclonal antibodies directed against Thy 1.1 antigen disulfide linked to two ribosomal inhibitors: pokeweed antiviral protein or ricin A chain.Cancer Res 44, 1398 (1984).PubMedGoogle Scholar
  52. 52.
    Seto M, Umemoto N, Saito M, Masuho Y, Hara T, Takahashi T: Monoclonal anti-MN46 antibody: ricin A chain conjugate:in vivo andin vitro antitumor activity.Cancer Res 42, 5209 (1982).PubMedGoogle Scholar
  53. 53.
    Kishida K, Masuho Y, Saito M, Hara T, Fuji H: Ricin A chain conjugated with monoclona anti-L1210 antibody.In vitro andin vivo antitumor activity.Cancer Immun Immunother 16, 93 (1983).Google Scholar
  54. 54.
    Bernhard M I, Foon K A, Oeltmann T N, Key M E, Hwang K M, Clarke G C, Christensen W L, Hoyer L C, Hanna M G, Oldham R K: Guinea pig line 10 hepatocarcinoma model: characterization of monoclonal antibody andin vivo effect of unconjugated antibody and antibody conjugated to diphtheria toxin A chain.Cancer Res 43, 4420 (1983).PubMedGoogle Scholar
  55. 55.
    Krolick K A, Uhr J W, Slavia S, Vitetta E S:In vivo therapy of a murine B cell tumor (BCL1) using antibody-ricin A chain immunotoxins.J Exp Med 155, 1797 (1982).PubMedCrossRefGoogle Scholar
  56. 56.
    Spitler L E: Phase I clinical trials with immunotoxins, in Vogel C W (ed.):Immunoconjugates: Antibody Conjugates in Radioimaging and Therapy of Cancer. New York, Oxford University Press (in press).Google Scholar
  57. 57.
    Spitler L S, del Rio M, Khentigan A, Wedel W I, Brophy N A, Miller L L, Harkonen W S, Rosendorf L L, Lee H M, Mischak R P, Kawahata R T, Stoudemire J B, Fradkin L B, Bautista E E, Scannon P J: Therapy of patients with malignant melanoma using a monoclonal antimelanoma antibody-ricin A chain immunotoxin.Cancer Res (in press).Google Scholar

Copyright information

© Humana Press Inc. 1986

Authors and Affiliations

  • Lynn E. Spitler
    • 1
  1. 1.Department of Medicine, Children's HospitalSan Francisco and XOMA CorporationBerkeleyU.S.A.

Personalised recommendations