ANTI-TYROSINASE ANTIBODIES PARTICIPATE IN THE IMMUNE-RESPONSE TO VACCINATION WITH ANTIIDIOTYPIC ANTIBODIES MIMICKING THE HIGH-MOLECULAR-WEIGHT MELANOMA-ASSOCIATED ANTIGEN

被引：12

作者：

BAHARAV, E ^{[1
]}

MERIMSKY, O ^{[1
]}

ALTOMONTE, M ^{[1
]}

SHOENFELD, Y ^{[1
]}

PAVLOVIC, M ^{[1
]}

MAIO, M ^{[1
]}

FERRONE, S ^{[1
]}

FISHMAN, P ^{[1
]}

机构：

[1] BEILINSON MED CTR,RES INST,IL-49100 PETAH TIQWA,ISRAEL

来源：

MELANOMA RESEARCH | 1995年 / 5卷 / 05期

关键词：

ANTI-TYROSINASE ANTIBODIES; ANTIIDIOTYPIC ANTIBODIES; VACCINATION;

D O I：

10.1097/00008390-199510000-00006

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Seven patients with metastatic melanoma were vaccinated with anti-idiotypic monoclonal antibody (mAb) MK2-23 which mimics the high-molecular-weight melanoma-associated antigen (HMW MAA), Sera samples were assayed for anti-anti-idiotypic antibodies, by Ab1-Ab2 complex inhibition test, for anti-Bls epitope antibodies, which are a heterogeneous group against various antigens presented on B16 melanoma cells and for anti-tyrosinase antibodies, which are specific against tyrosinase. Our results pointed to the participation of anti-tyrosinase antibodies in the immune response to vaccination by antiidiotypic antibodies mimicking the HMW MAA. The antityrosinase antibody kinetic curves presented an initial increase in titres in five cases followed by decreasing titres; in two cases a constant decrease was noted. The inhibition assay demonstrated an increasing percentage of inhibition (range 17-100%) within 100-400 days of treatment, The titre of the anti-tyrosinase antibodies increased following the vaccination, then decreased - probably due to absorption of the antibodies to melanoma cells and normal melanocytes. A positive slope in the percentage of inhibition was roughly associated with a negative slope of anti-tyrosinase antibodies. In one case, a long-standing complete clinical response was accompanied by development of melanoma-associated hypopigmentation. Anti-ale epitope antibodies had no role in the response to vaccination, The development of anti-tyrosinase antibodies in response to vaccination by anti-idiotypic antibodies mimicking another antigen may be explained by induction of non-specific polyclonal B lymphocytes activation, a well-recognized phenomenon in autoimmune disorders, While in autoimmune diseases the production of a second autoantibody may aggravate the course, in melanoma it may contribute to the regression of the disease in some patients.

引用

页码：337 / 343

页数：7

共 24 条

[1]

Merimsky O., Shoenfeld Y., Chaitchik S., Et al., Antigens and antibodies in malignant melanoma, Tumor Biol, 15, pp. 188-202, (1994)

[2]

Ferrane S., Kageshita T., High-molecular weight melanoma associated antigen as a target for active specific immunotherapy: A phase I clinical trial with murine monoclonal antibodies, J Dermatol, 15, pp. 457-465, (1988)

[3]

Mittelman A., Chen Z.J., Kageshita T., Et al., Active specific immunotherapy in patients with melanoma: A clinical trial with minimal anti-idiotypic monoclonal antibodies elicited with synergistic anti-high-molecular weight melanoma associated antigen monoclonal antibodies, J Clin Invest, 86, pp. 2136-2144, (1990)

[4]

Mittleman A., Chen Z.J., Yang H., Et al., 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, pp. 466-470, (1992)

[5]

Thampose I.J., Furukawa K., Velie E., Et al., Sialyltransferase levels and ganglioside expression in melanoma and other cultured cancer cells, Cancer Res, 49, pp. 7045-7050, (1989)

[6]

Lewis M.G., Ikonopisov R.L., Nairn R.C., Et al., Tumor-specific antibodies in human malignant melanoma and their relationship to the extent of the disease, Br Med J, 3, pp. 547-552, (1969)

[7]

Merimsky O., Shoenfeld Y., Yecheskel G., Et al., Vitiligo and melanoma associated hypopigmentation: A similar appearance but a different mechanism, Cancer Immunol Immunother, 38, pp. 411-416, (1994)

[8]

Shibahara S., Tornita Y., Sakahura T., Et al., Cloning and expression of cDNA encoding mouse tyrosinase, Nucl Acids Res, 14, pp. 2413-2427, (1986)

[9]

Jimenez M., Lee Maloy W., Hearing V.J., Specific identification of an authentic clone for mammalian tyrosinase, J Biol Chem, 264, pp. 3397-3403, (1989)

[10]

Yamamoto H., Takeuchi S., Kudo T., Et al., Melanin production in cultured albino melanocytes transfected with mouse tyrosinase cDNA, Jpn J Genet, 64, pp. 121-135, (1989)

← 1 2 3 →