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Handbook of Cancer Vaccines pp 275–296Cite as

Hapten-Modified Tumor Vaccines

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Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

Abstract

Haptens are tiny lights that illuminate the dark recesses of the immune system. They were discovered by Karl Landsteiner, who used haptens to explore the breadth and fine sensitivity of antibody responses. Landsteiner (1) worked with a variety of simple chemicals, including nitrophenyls and phenyl arsonates, that were incapable of inducing an immune response by themselves, but became immunogenic when they were attached covalently to a protein carrier. He coined the term “hapten” from the Greek haptein, meaning to fasten.

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References

  1. Landsteiner K. Artificial conjugated antigens. Serological reactions with simple chemical compounds. In: Anonymous. The specificity of serological reactions. New York: Dover, 1962:156–209.

    Google Scholar 

  2. Landsteiner K, van der Scheer J. On cross reactions of immune sera to azoproteins. J Exp Med 1936; 63:325.

    Article  PubMed  CAS  Google Scholar 

  3. Weigle WO. Termination of immunologic unresponsiveness. In: Weigle WO, ed. Natural and acquired immunologic unresponsiveness. Cleveland: World Publishing, 1967:57–173.

    Google Scholar 

  4. Geczy AF, Baumgarten A. Lymphocyte transformation in contact sensitivity. Immunology 1970; 19:189–203.

    PubMed  CAS  Google Scholar 

  5. Raff MC. Surface antigenic markers for distinguishing T and B lymphocytes in mice. Transplant Res 1971; 6:52.

    CAS  Google Scholar 

  6. Rubin B, Wigzell H. The immune response against hapten-autologous protein conjugates in the mouse. J Exp Med 1973; 137:911–931.

    Article  PubMed  CAS  Google Scholar 

  7. Shearer GM. Cell-mediated cytotoxicity to trinitrophenyl-modified syngeneic lymphocytes. Eur J Immunol 1974; 4:527–533.

    Article  PubMed  CAS  Google Scholar 

  8. Fujiwara M, Fujiwara S. Mechanism of termination of immunological tolerance. Immunology 1975; 29:1171–1179.

    PubMed  CAS  Google Scholar 

  9. Tarcic N, David CS, Naor D. Auto-delayed-type hypersensitivity induced in immunodeficient mice with modified self-antigens. V. Cellular autoreactivity directed against self-H-2Dd subregion mediates the inflammatory responses. Immunology 1989; 67:184–190.

    PubMed  CAS  Google Scholar 

  10. Little JR, Eisen HN. Preparation of immunogenic 2,4-dinitrophenyl and 2,4,6-trinitrophenyl proteins. In: Williams CA, Chase MW, eds. Methods in immunology and immunochemistry. New York: Academic, 1967:128–132.

    Google Scholar 

  11. Henkart PA, Schmitt-Verhulst A-M, Shearer GM. Specificity of cytotoxic effector cells directed against trinitrobenzene sulfonate-modified syngeneic cells. Failure to recognize cell surface-bound trinitrophenyl dextran. J Exp Med 1977; 146:1068–1078.

    Article  PubMed  CAS  Google Scholar 

  12. Sherman LA, Burakoff SJ, Benaceraff B. The induction of cytolytic T lymphocytes with specificity for p-azophenylarsonate coupled syngeneic cells. J Immunol 1978; 121:1432–1436.

    PubMed  CAS  Google Scholar 

  13. Hanna N, Jarosch E, Leskowitz S. Altered immunogenicity produced by change in mode of linkage of hapten to carrier. Proc Soc Exp Biol Med 1972; 140:89–92.

    PubMed  CAS  Google Scholar 

  14. Levy RB, Shearer GM, Richardson JC, Henkart PA. Cell-mediated lympholytic responses against autologous cells modified with haptenic sulfhydryl reagents. I. Effector cells can recognize two distinct classes of hapten-reactive self sites on cell surface proteins. J Immunol 1981; 127:523.

    PubMed  CAS  Google Scholar 

  15. Ortmann B, Martin S, Von Bonin A, Schiltz E, Hoschüitzky H, Weltzien HU. Synthetic peptides anchor T cell-specific TNP epitopes to MHC antigens. J Immunol 1992; 148:1445–1450.

    PubMed  CAS  Google Scholar 

  16. Martin S, Ortmann B, Pflugfelder U, Birsner U, Weltzien HU. Role of hapten-anchoring peptides in defining hapten-epitopes for MHC-restricted cytotoxic T cells: cross-reactive TNP-determinants on different peptides. J Immunol 1992; 149:2569–2575.

    PubMed  CAS  Google Scholar 

  17. Von Bonin A, Ortmann B, Martin S, Weltzien HU. Peptide-conjugated hapten groups are the major antigenic determinants for trinitrophenyl-specific cytotoxic cells. Int Immunol 1992; 4:869–874.

    Article  Google Scholar 

  18. Cavani A, Hackett CJ, Wilson KJ, Rothbard JB, Katz SI. Characterization of epitopes recognized by hapten-specific CD4+ T cells. J Immunol 1995; 154:1232–1238.

    PubMed  CAS  Google Scholar 

  19. Kim BS, Jang YS. Constraints in antigen processing result in unresponsiveness to a T cell epitope of hen egg lysozyme in C57BL/6 mice. Eur J Immunol 1992; 22:775–782.

    Article  PubMed  CAS  Google Scholar 

  20. Neurath MF, Fuss I, Kelsall BL, Stuber E, Strober W. Antibodies to interleukin 12 abrogate established experimental colitis in mice. J Exp Med 1995; 182:1281–1290.

    Article  PubMed  CAS  Google Scholar 

  21. Rennke HG, Klein PS, Sandstrom DJ, Mendrick DL. Cell-mediated immune injury in the kidney: acute nephritis induced in the rat by azobenzenearsonate. Kidney Int 1994; 45:1044–1056.

    Article  PubMed  CAS  Google Scholar 

  22. deWeck AL. Pharmacologic and immunochemical mechanisms of drug hypersensitivity. Immunol All Clin NA 1991; 11:461–474.

    Google Scholar 

  23. Tsutsui H, Terano Y, Sakagami C, Hasegawa I, Mizoguchi Y, Morisawa S. Drugspecific T cells derived from patients with drug-induced allergic hepatitis. J Immunol 1992; 149:706–716.

    PubMed  CAS  Google Scholar 

  24. Gilliland BC. Drug-induced autoimmune and hematologic disorders. Immunol Allergy Clin North Am 1991; 11:525–553.

    Google Scholar 

  25. Mullen CA, Urban JL, Van Waes C, Rowley DA, Schreiber H. Multiple cancers. Tumor burden permits the outgrowth of other cancers. J Exp Med 1985; 162:1665–1682.

    Article  PubMed  CAS  Google Scholar 

  26. Flood PM, Schreiber H, Ron Y. Protective immunity to progressive tumors can be induced by antigen presented on regressor tumors. J Immunol 1987; 138:3573–3579.

    PubMed  CAS  Google Scholar 

  27. Mitchison NA. Immunologic approach to cancer. Transplant Proc 1970; 11:92–103.

    Google Scholar 

  28. Cavallo G, Forni G. Cell reactivity toward syngeneic neoplastic cells in mice hypersensitized to DNP. Eur J Cancer 1974; 10:103–106.

    Article  PubMed  CAS  Google Scholar 

  29. Galili N, Naor D, Asjo B, Klein G. Induction of immune responsiveness in a genetically low-responsive tumor-host combination by chemical modification of the immunogen. EurJ Immunol 1976; 6:473–476.

    Article  CAS  Google Scholar 

  30. Roth JA, Morton DL, Holmes EC. Rejection of dinitrochlorobenzene-conjugated syngeneic tumor cells by dinitrochlorobenzene-sensitized guinea pigs. J Surg Res 1978; 25:1–7.

    Article  PubMed  CAS  Google Scholar 

  31. Bauminger S, Yachnin S. Unimpeded growth of tumour in hosts pre-immunized with tyrosyl- or dinitrophenyl-coated tumour cells. Br J Cancer 1972; 26:77–83.

    Article  PubMed  CAS  Google Scholar 

  32. Fujiwara H, Aoki H, Yoshioka T, Tomita S, Ikegami R, Hamaoka T. Establishment of a tumor-specific immunotherapy model utilizing TNP-reactive helper cell activity and its application to the autochthonous tumor system. J Immunol 1984; 133:509–514.

    PubMed  CAS  Google Scholar 

  33. Sojka DK, Felnerova D, Mokyr MB. Anti-metastatic activity of hapten-modified autologous tumor cell vaccine in an animal tumor model. Cancer Immunol Immunother 2002; 51:200–208.

    Article  PubMed  CAS  Google Scholar 

  34. Maguire HC, Jr., Ettore VL. Enhancement of dinitrochlorobenzene (DNCB) contact sensitization by cyclophosphamide in the guinea pig. J Invest Dermatol 1967; 48:39–42.

    PubMed  CAS  Google Scholar 

  35. Berd D, Mastrangelo MJ, Engstrom PF, Paul A, Maguire H. Augmentation of the human immune response by cyclophosphamide. Cancer Res 1982; 42:4862–4866.

    PubMed  CAS  Google Scholar 

  36. Prehn RT, Main JM. Immunity to methylcholanthrene-induced sarcomas. J Nat! Cancer Inst 1957; 18:769–778.

    PubMed  CAS  Google Scholar 

  37. Basombrio MA. Search for common antigenicities among twenty-five sarcomas induced by methylcholanthrene. Cancer Res 1970; 30:2458–2462.

    PubMed  CAS  Google Scholar 

  38. Srivastava PK, Old L. Individually distinct transplantation antigens of chemically induced mouse tumors. Immunol Today 1988; 9:78–83.

    Article  PubMed  CAS  Google Scholar 

  39. Ramarathinam L, Sarma S, Maric M, Zhao M, Yang G, Chen LP, et al. Multiple lineages of tumors express a common tumor antigen, P1 A, but they are not cross-protected. J Immunol 1995; 155:5323–5329.

    PubMed  CAS  Google Scholar 

  40. Hengst JCD, Mokyr MB, Dray S. Importance of timing in cyclophosphamide therapy of MOPC-315 tumor-bearing mice. Cancer Res 1980; 40:2135–2141.

    PubMed  CAS  Google Scholar 

  41. North RJ. Cyclophosphamide-facilitated adoptive immunotherapy of an established tumor depends on elimination of tumor-induced suppressor T cells. J Exp Med 1982; 55:1063–1074.

    Article  Google Scholar 

  42. Catalona WJ, Taylor PT, Chretien PB. Quantitative dinitrochlorobenzene contact sensitization in a normal population. Clin Exp Immunol 1972; 12:325–333.

    PubMed  CAS  Google Scholar 

  43. Miller AE, Levis WR. Lymphocyte transformation during dinitrochlorobenzene contact sensitization. J Clin Invest 1973; 52:1925–1930.

    Article  PubMed  CAS  Google Scholar 

  44. Miller SD, Claman HN. The induction of hapten-specific T cell tolerance by using hapten-modified lymphoid cells. I. Characteristics of tolerance induction. J Immunol 1976; 117:1519–1526.

    PubMed  CAS  Google Scholar 

  45. Berd D, Maguire HC, Jr., Mastrangelo MJ. Induction of cell-mediated immunity to autologous melanoma cells and regression of metastases after treatment with a melanoma cell vaccine preceded by cyclophosphamide. Cancer Res 1986; 46:2572–2577.

    PubMed  CAS  Google Scholar 

  46. Sato T, Maguire HC, Jr., Mastrangelo MJ, Berd D. Human immune response to DNP-modified autologous cells after treatment with a DNP-conjugated melanoma vaccine. Clin Immunol Immunopathol 1995; 74(1):35–43.

    Article  PubMed  CAS  Google Scholar 

  47. Sato T, Bullock TNJ, Eisenlohr LC, Mastrangelo MJ, Berd D. Dinitrophenyl-modified autologous melanoma vaccine induces a T cell response to hapten-modified, melanoma peptides. Clin Immunol Immunopathol 1997; 85:265–272.

    Article  PubMed  CAS  Google Scholar 

  48. Berd D, Sato T, Cohn H, Maguire HC, Jr., Mastrangelo MJ. Treatment of metastatic melanoma with autologous, hapten-modified melanoma vaccine: regression of pulmonary metastases. Int J Cancer 2001; 94:531–539.

    Article  PubMed  CAS  Google Scholar 

  49. Berd D, Maguire HC, Jr., Schuchter LM, Hamilton T, Hauck WW, Sato T, et al. Autologous, haptenmodified melanoma vaccine as post-surgical adjuvant treatment after resection of nodal metastases. J Clin Oncol 1997; 15:2359–2370.

    PubMed  CAS  Google Scholar 

  50. Berd D, Murphy G, Maguire HC, Jr., Mastrangelo MJ. Immunization with haptenized, autologous tumor cells induces inflammation of human melanoma metastases. Cancer Res 1991; 51:2731–2734.

    PubMed  CAS  Google Scholar 

  51. Berd D, Maguire HC, Jr., Mastrangelo MJ, Murphy GF. Activation markers on T cells infiltrating melanoma metastases after therapy with dinitrophenyl-conjugated vaccine. Cancer Immunol Immunother 1994; 39:141–147.

    Article  PubMed  CAS  Google Scholar 

  52. Evans R, Faldetta TJ, Humphreys RE, Pratt DM, Yunis EJ, Schlossman SF. Peripheral human T cells sensitized in mixed leukocyte culture synthesize and express Ia-like antigens. J Exp Med 1978; 148:1440–1445.

    Article  PubMed  CAS  Google Scholar 

  53. Testi R, Phillips JH, Lanier LL. T cell activation via Leu-23 (CD69). J Immunol 1989; 143:1123–1128.

    PubMed  CAS  Google Scholar 

  54. Lattime EC, Mastrangelo MJ, Bagasra O, Li W, Berd D. Expression of cytokine mRNA in human melanoma tissues. Cancer Immunol Immunother 1995; 41:151–156.

    Article  PubMed  CAS  Google Scholar 

  55. Sensi ML, Farina C, Maccalli C, Lupetti R, Nicolini G, Anichini A, et al. Clonal expansion of T lymphocytes in human melanoma metastases after treatment with a hapten-modified autologous tumor vaccine. J Clin Invest 1997; 99:710–717.

    Article  PubMed  CAS  Google Scholar 

  56. Manne J, Mastrangelo MJ, Sato T, Berd D. T cell receptor rearrangement in lymphocytes infiltrating melanoma metastases after administration of autologous dinitrophenyl-modified vaccine. J Immunol 2002; 169:3407–3412.

    PubMed  CAS  Google Scholar 

  57. Coit DG, Rogatko A, Brennan MF. Prognostic factors in patients with melanoma metastatic to axillary or inguinal lymph nodes: a multivariate analysis. Ann Surg 1991; 214:627–636.

    Article  PubMed  CAS  Google Scholar 

  58. Balch CM, Soong S-J, Gershenwald JE, Thompson JF, Reintgen DS, Cascinelli N, et al. Prognostic factors analysis of 17,600 melanoma patients: validation of the American Joint Committee on Cancer melanoma staging system. J Clin Oncol 2001; 19:3622–3634.

    PubMed  CAS  Google Scholar 

  59. Kirkwood JM, Strawderman MH, Ernstoff MS, Smith TJ, Borden EC, Blum RH. Interferon alfa-2b adjuvant therapy of high-risk resected cutaneous melanoma: the Eastern Cooperative Oncology Group trial EST 1684. J Clin Oncol 1996; 14:7–17.

    PubMed  CAS  Google Scholar 

  60. Kirkwood JM, Ibrahim JG, Sosman JA, Sondak VK, Agarwala SS, Ernstoff MS, et al. High-dose interferon alfa-2b significantly prolongs relapse-free and overall survival compared with the GM2KLH/QS-21 vaccine in patients with resected stage IIB-Ill melanoma: results of intergroup trial E1694/ 59512/C509801. J Clin Oncol 2001; 19:2370–2380.

    PubMed  CAS  Google Scholar 

  61. Berd D, Sato T, Mastrangelo MJ. Effect of the dose and composition of an autologous, hapten-modified melanoma vaccine on the development of delayed-type hypersensitivity responses. Cancer Immunol Immunother 2002; 51:320–326.

    Article  PubMed  CAS  Google Scholar 

  62. Berd D, Mastrangelo MJ, Sato T, Bloome E. Effectiveness of autologous, hapten-modified melanoma vaccine depends on the timing of an induction dose. Proc Am Assoc Cancer Res 2001; 42:683 (Abstract).

    Google Scholar 

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Authors
  1. David Berd MD
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Editors and Affiliations

  1. Duke University Medical Center, Durham, NC, USA

    Michael A. Morse MD , Timothy M. Clay PhD  & H. Kim Lyerly MD ,  & 

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© 2004 Humana Press Inc.

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Berd, D. (2004). Hapten-Modified Tumor Vaccines. In: Morse, M.A., Clay, T.M., Lyerly, H.K. (eds) Handbook of Cancer Vaccines. Cancer Drug Discovery and Development. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-680-5_19

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  • DOI: https://doi.org/10.1007/978-1-59259-680-5_19

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-4684-9818-9

  • Online ISBN: 978-1-59259-680-5

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