Active Specific Immunotherapy of Malignant Melanoma and Peptide Mimics of the Human High-Molecular-Weight Melanoma-Associated Antigen
The realization that tumor cells utilize multiple mechanisms to escape from immune recognition and destruction has stimulated interest in developing and applying immunotherapeutic strategies which target both humoral and cellular immunity to malignant cells. As a result, the tumor-associated antigens (TAA) used as targets have to be expressed on the cell surface membrane of malignant cells. Furthermore, since most of the TAA used for active specific immunotherapy are self-antigens, a challenge facing tumor immunologists is to develop strategies which are effective in breaking tolerance to self-antigens. This chapter describes one strategy which relies on the use of peptide mimics of the human high-molecular-weight melanoma-associated antigen (HMW-MAA) as immunogens to implement active specific immunotherapy in patients with malignant melanoma. These mimics, which are isolated from phage display peptide libraries by panning with anti-HMW-MAA monoclonal antibodies, are expected to induce both humoral and cellular anti-HMW-MAA immunity.
KeywordsActive Specific Immunotherapy Phage Display Peptide Library Acral Lentiginous Melanoma Peptide Mimic Human High Molecular Weight
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- 8.Marincola FM, Jaffee EM, Hicklin DJ, Ferrone S (1999) Escape of human solid tumors from T cell recognition: molecular mechanisms and functional significance. Adv Immunol In pressGoogle Scholar
- 9.Mittelman A, Chen ZJ, Yang H, Wong GY, Ferrone S (1992) Human high molecular weight melanoma-associated antigen (HMW-MAA) mimicry by mouse anti-idiotypic monoclonal antibody MK2–23: Induction of humoral anti-HMW-MAA immunity and prolongation of survival in patients with stage IV melanoma. Proc Natl Acad Sci USA 89: 466–470PubMedCrossRefGoogle Scholar
- 10.Livingston PO, Wong GY, Adluri S, Tao Y, Padavan M, Parente R, Hanlon C, Calves MJ, Helling F, Ritter G, Oettgen HF, Old LJ (1994) Improved survival in AJCC stage III melanoma patients with GM2 antibodies: A randomized trial of adjuvant vaccination with GM2 ganglioside. J Clin Oncol 12: 1036–1044PubMedGoogle Scholar
- 12.Riethmuller G, Schneider-Gadicke E, Schlimok G, Schmiegel W, Raab R, Hoffken K, Gruber R, Pichlmaier H, Hirche H, Pichlmayr R, Buggisch P, Witte J and the German Cancer Aid 17–1A study group (1994) Randomised trial of monocloncal antibody for adjuvant therapy of resected Dukes’ C colorectal carcinoma. Lancet 343: 1177–1183PubMedCrossRefGoogle Scholar
- 13.Pegram MD, Lipton A, Hayes DF, Weber BL, Baselga JM, Tripathy D, Baly D, Baughman SA, Twadddell T, Glaspy JA, Slamon DJ (1998) Phase II study of receptor-enhanced chemosensitivity using recombinant humanized anti-pl85HER2/neu monoclonal antibody plus cisplatin in patients with HER/2neu-overexpressing metastatic breast cancer refractory to chemotherapy treatment. J Clin Oncol 16: 2659–2671PubMedGoogle Scholar
- 14.Mendelsohn J, Shin DM, Donato N, Khuri F, Radinsky R, Glisson BS, Shin HJ, Metz E, Pfister D, Perez-Soler R, Lawhorn K, Matsumoto T, Gunnett K, Falcey J, Waksal H, Hong WK (1999) A phase I study of chimerized anti-epidermal growth factor receptor (EGFr) monoclonal antibody, C225, in combination with cisplatin (CDDP) in patients (PTS) with recurrent head and neck squamous cell carcinoma ( SCC ). Proc Am Soc Clin Oncol 18: 389aGoogle Scholar
- 19.Ferrone S, Temponi M, Gargiulo D, Scassellati GA, Cavaliere R, Natali PG (1988) Selection and utilization of monoclonal antibody defined melanoma associated antigens for immunoscintigraphy in patients with melanoma. In: Radiolabeled monoclonal antibodies for imaging and therapy, NATO ASI Series, ( Srivastava, SC, ed) Plenum Press New York and London 152: 55–78Google Scholar
- 20.Giacomini P, Natali PG, Ferrone 5 (1985) Analysis of the interaction between a human high molecular weight melanoma-associated antigen and the monoclonal antibodies to three distinct antigenic determinants. J Immunol 135: 696–702Google Scholar
- 21.Chattopadhyay P, Kaveri S-V, Byars N, Starkey J, Ferrone S, Raychaudhuri S (1991) Human high molecular weight-melanoma associated antigen mimicry by an anti-idiotypic antibody: Characterization of the immunogenicity and the immune response to the mouse monoclonal antibody IMEL-1. Cancer Res 51: 6045–6051PubMedGoogle Scholar
- 22.Kageshita T, Kuriya N, Ono T, Horikoshi T, Takahashi M, Wong GY, Ferrone S (1993) Association of high molecular weight melanoma-associated antigen expression in primary acral lentiginous melanoma lesions with poor prognosis. Cancer Res 53: 2830–2833Google Scholar
- 23.Schlingemann RO, Rietveld FJR, de Waal RMW, Ferrone S, Ruiter DJ (1990) Expression of the high molecular weight melanoma-associated antigen by pericytes during angiogenesis in tumors and in healing wounds. Am J Pathol 136: 1393–1405Google Scholar