Abstract
We have developed a partially purified, polyvalent melanoma vaccine from surface material shed into culture medium by a pool of selected melanoma cells. The vaccine contains a broad spectrum of melanoma antigens to circumvent the antigenic heterogeneity of melanoma and to obviate the need to identify individual antigens that mediate tumor-protective immunity.
Vaccine treatment augments antimelanoma humoral and/or cellular immunity in over 50% of patients and can increase immunity to a patient’s own melanoma. Vaccine-induced antibodies are directed at one or more surface antigens with molecular masses of 210, 150, 110, 75, or 38kDa. The 210- and 110-kDa antigens are melanoma associated, as they were expressed by four of five human melanoma cell lines, but by only two of 12 control cell lines, and are unrelated to previously described melanoma antigens.
The disease-free (DF) and overall survival (OS) of vaccine-treated patients with surgically resected stage II (regional) disease is 50% longer than that of historical controls. Survival is particularly prolonged in patients who develop an immune response. Median DF survival is 4.7 years longer and OS 3.7 years longer in patients with a strong, as opposed to no, cellular immune response to vaccine treatment (p = <0.02). Similarly, median DF survival of patients with vaccine-induced melanoma antibodies is significantly longer than that of nonresponders (65 months vs. 17 months, respectively), as is overall survival (p = 0.01). These differences in outcome are unrelated to disease severity or to the overall immunological competence of the patients, suggesting they result from vaccine treatment.
Thus melanoma vaccine treatment is safe, capable of stimulating antimelanoma immunity in many patients, and appears to be clinically effective in delaying the progression of this cancer in some individuals.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
Similar content being viewed by others
References
Adler A, Oratz R, Liebes L, Bystryn J-C (1990) Effect of allogeneic melanoma vaccine on the in vitro cellular immune response. Proc Am Assoc Cancer Res 31:252
Balch CM, Soong S-J, Shaw HM (1985) A comparison of world-wide melanoma data. In: Shaw HM, Seng-Jaw S (eds) Cutaneous melanoma. Lippincott, Philadelphia, pp 507–518
Berdeaux DH, Meyskens FL Jr, Parks B et al (1989) Cutaneous malignant melanoma. II. The natural history and prognostic factors influencing the development of stage II disease. Cancer 63:1430–1436
Bystryn J-C (1978) Antibody response and tumor growth in syngeneic mice immunized to partially purified B16 melanoma associated antigens. J Immunol 120:96–101
Bystryn J-C (1990) Tumor vaccines. Cancer Metastasis Rev 9:81–91
Bystryn J-C (1992) Identification of immunogenic human melanoma antigens in a polyvalent melanoma vaccine. Cancer Res 52:5948–5953
Bystryn J-C (1993) Immunogenicity and clinical activity of a polyvalent melanoma antigen vaccine prepared from shed antigens. In: Bystryn J-C, Ferrone S, Livingston P (eds) Specific immunotherapy of cancer with vaccines. Ann NY Acad Sci 690:190–203
Bystryn J-C, Tedholm CA, Heaney-Kieras J (1981) Release of surface macro-molecules by human melanoma and normal cells. Cancer Res 41:910–914
Bystryn J-C, Jacobsen S, Harris MN, Roses DF, Speyer JL, Levin M (1986) Preparation and characterization of a polyvalent human melanoma antigen vaccine. J Biol Response Mod 5:221–224
Bystryn J-C, Oratz R, Harris MN, Roses DF, Golomb FM, Speyer JL (1988) Immunogenicity of a polyvalent melanoma antigen vaccine in man. Cancer 61:1065–1070
Bystryn J-C, Dugan M, Oratz R, Speyer J, Harris MN, Roses DF (1989) Vaccine immunotherapy of human malignant melanoma: relationship between method of immunization, immunogenicity, and tumor progression. In: Fred Fox C (ed) Human tumor antigens and specific tumor therapy. Liss, New York, pp 307–315
Bystryn J-C, Oratz R, Roses DF, Harris MN, Henn M, Lew R (1991) Improved survival of melanoma patients with delayed type hypersensitivity response to melanoma vaccine immunization. Clin Res 39:503A
Bystryn J-C, Oratz R, Henn M, Adler A, Harris MN, Roses DF (1992) Relationship between immune response to melanoma vaccine and clinical outcome in stage II malignant melanoma. Cancer 69:1157–1164
Cui J, Oratz R, Harris M, Roses D, Henn M, Bystryn J-C (1992) Induction of cytolytic melanoma antibodies by immunization to a polyvalent melanoma antigen vaccine. Proc Am Assoc Cancer Res 32:256
Oratz R, Cockerall C, Speyer J, Harris MN, Roses DF, Bystryn J-C (1989) Induction of tumor-infiltrating lymphocytes in malignant melanoma metastasis by immunization to melanoma antigen vaccine. J Biol Response Mod 8:355–358
Oratz R, Dugan M, Roses DF, Harris MN, Speyer JL, Hochster H, Weissman J, Henn M, Bystryn J-C (1991) Lack of effect of cyclophosphamide on the immunogenicity of a melanoma antigen vaccine. Cancer Res 51:3643–3647
Schultz N, Oratz R, Chen D, Bystryn J-C (1992) Effect of DETOX on the immunogenicity of a polyvalent melanoma antigen vaccine in man. Proc Am Soc Clin Oncol 11:1180
Veronesi U, Adamus J, Aubert C et al (1982) A randomized trial of adjuvant chemotherapy and immunotherapy in cutaneous melanoma. N Engl J Med 307: 913–916
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1995 Springer-Verlag Berlin · Heidelberg
About this paper
Cite this paper
Bystryn, JC. (1995). Clinical Activity of a Polyvalent Melanoma Antigen Vaccine. In: Garbe, C., Schmitz, S., Orfanos, C.E. (eds) Skin Cancer: Basic Science, Clinical Research and Treatment. Recent Results in Cancer Research, vol 139. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-78771-3_26
Download citation
DOI: https://doi.org/10.1007/978-3-642-78771-3_26
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-78773-7
Online ISBN: 978-3-642-78771-3
eBook Packages: Springer Book Archive