Abstract
In this study, a human melanoma vaccine induced antibody responses in mice that varied significantly from animal to animal. BALB/c mice were immunized to a xenogenic human polyvalent melanoma vaccine that has been used in phase II clinical trials in over 600 patients. Mice were bled biweekly for up to 6 weeks to measure antibody responses. IgG antibody responses to the melanoma vaccine components were detectable within 2 weeks but were much stronger at 4 and 6 weeks. When the pooled sera were further analyzed by Western blot, a complex pattern of antigens was detected. When individual sera from identically immunized mice were assayed by Western blot, a consistent, reproducible pattern of antigen recognition was not seen. Rather, we found significantly different antibody responses among the mice. Both the intensity of antibody responses and the pattern of antigens recognized varied from animal to animal. Although there appeared to be immunodominant antigens that produced antibody responses in most mice, no single antigen induced antibody responses in all mice. These results demonstrate that polyvalent vaccines induce heterogeneous antibody responses in mice treated identically. Analysis of the response of selected melanoma patients immunized to the same vaccine revealed similar antibody responses to the antigens in the melanoma vaccine. Heterogeneity may hamper interpretation of vaccine immunogenicity and relevant tumor antigens in humans.
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References
Bystryn J-C, Shapiro RL, Oratz R (1995) Cancer vaccines: clinical applications: partially purified tumor antigen vaccines. In: DeVita V, Hellman S, Rosenberg SA (eds) Biologic therapy of cancer, 2nd edn. Lippincott, Philadelphia, pp 668–679
Bystryn J-C, Oratz R, Shapiro RL, Harris MN, Roses DF, Zeleniuch-Jacquotte A, Chen DL, Rivas MC (1999) Double-blind, placebo-controlled trial of a shed, polyvalent, melanoma vaccine in stage III melanoma. Proc Am Soc Clin Oncol 434:1673
DiFronzo LA, Gupta RK, Essner R, Foshag LJ, O‘Day SJ, Wanek LA, Stern SL, Morton DL (2002) Enhanced humoral immune response correlates with improved disease-free and overall survival in American joint committee on cancer stage II melanoma patients receiving adjuvant polyvalent vaccine. J Clin Oncol 20:3242–3248
Finn OJ (2003) Cancer vaccines: between the idea and the reality. Nat Rev Immunol 8:630–641
Gross DA, Graff-Dubois S, Opolon P, Cornet S, Alves P, Bennaceur-Griscelli A, Faure O, Guillaume P, Firat H, Chouaib S, Lemonnier FA, Davoust J, Miconnet I, Vonderheide RH, Kosmatopoulos K (2004) High vaccination efficiency of low-affinity epitopes in antitumor immunotherapy. J Clin Invest 113:425–433
Hsueh EC, Essner R, Foshag LJ, Ye W, Morton DL (2002) Active immunotherapy by reinduction with a polyvalent allogeneic cell vaccine correlates with improved survival in recurrent metastatic melanoma. Ann Surg Oncol 5:486–492
Keilholz U, Weber J, Finke JH, Gabrilovich DI, Kast WM, Disis ML, Kirkwood JM, Scheibenbogen C, Schlom J, Maino VC, Lyerly HK, Lee PP, Storkus W, Marincola F, Worobec A, Atkins MB (2002) Immunologic monitoring of cancer vaccine therapy: results of a workshop sponsored by the society for biological therapy. J Immunother 15:97–138
Livingston P (2001) The unfulfilled promise of melanoma vaccines. Clin Cancer Res 7:1837–1838
Miller K, Abeles G, Oratz R, Zeleniuch-Jacquotte A, Cui J, Roses DF, Harris M, Bystryn J-C (1995) Improved survival of melanoma patients with an antibody response to immunization to a polyvalent melanoma vaccine. Cancer 75(2):495–502
Reynolds SR, Oratz R, Shapiro RL, Fotino M, Hao P, Vukmanovic S, Bystryn J-C (1997) Stimulation of CD8+ T cell responses to MAGE-3 and MELAN A/MART-1 by immunization to a polyvalent melanoma vaccine. Int J Cancer 72:1–5
Reynolds SR, Celis E, Sette A, Oratz R, Shapiro RL, Johnston D, Fotino M, Bystryn J-C (1998) HLA-independent heterogeneity of CD8+ T cell responses to MAGE-3, Melan A/MART-1, gp100, tyrosinase, MC1R and TRP-2 in vaccine-treated melanoma patients. J Immunol 161:6970–6976
Shapiro RL, Johnston D, Oratz R, Harris MN, Roses DF, Zeleniuch-Jacquotte A, Beck A, Bystryn J-C (1999) Effect of GM-CSF liposomes on the immunogenicity of a polyvalent melanoma vaccine. Proc Am Soc Clin Oncol 440:1695
Shen HD, Choo KB, Lin WL, Lin RY, Han SH (1990) An improved scheme for the identification of antigens recognized by specific antibodies in two-dimensional gel electrophoresis and immunoblotting. Electrophoresis 11:878–882
Slingluff CL Jr, Petroni GR, Yamshchikov GV, Barnd DL, Eastham S, Galavotti H, Patterson JW, Deacon DH, Hibbits S, Teates D, Neese PY, Grosh WW, Chianese-Bullock KA, Woodson EMH, Wiernasz CJ, Merrill P, Gibson J, Ross M, Engelhard VH (2003) Clinical and immunological results of a randomized phase II trial of vaccination using four melanoma peptides either administered in granulocyte–macrophage colony-stimulating factor in adjuvant or pulsed on dendritic cells. J Clin Oncol 21:4016–4026
Sosman JA, Weeraratna AT, Sondak VK (2004) When will melanoma vaccines be proven effective? J Clin Oncol 22:1–3
Tjoa BA, Elgamal A-AA, Murphy GP (1999) Vaccine therapy for prostate cancer. Urol Clin North Am 26(2):365–374
Zhang S, Zhang HS, Reuter VE, Slovin SF, Scher HI, Livingston PO (1998) Expression of potential target antigens for immunotherapy on primary and metastatic prostate cancers. Clin Can Res 4:295–302
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This research was supported in part by grant CA096804 (to DJ) from the National Institutes of Health.
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Johnston, D., Bystryn, JC. Heterogeneous antibody response to polyvalent melanoma vaccines in syngeneic mice. Cancer Immunol Immunother 54, 345–350 (2005). https://doi.org/10.1007/s00262-004-0606-9
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DOI: https://doi.org/10.1007/s00262-004-0606-9