ANALYSIS OF MELANOMA IDIOTYPE NETWORK AND IT'S APPLICATION FOR VACCINE THERAPY.

黑色素瘤独特型网络分析及其在疫苗治疗中的应用。

基本信息

批准号：
07670952
负责人：
KAGESHITA Toshiro
金额：
$ 1.47万
依托单位：
KUMAMOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07670952/
关键词：
MELANOMA HLA CLASS I IDIOTYPE NETWORK ANTI-IDIOTYPIC MONOCLONAL ANTIBODY HLA class1

项目摘要

(1) Immunohistochemical analysis of idiotype network in melanomaThe mouse anti-id mAb MK2-23 bears the internal image of the antigenic determinant defined by anti-HMW-MAA mAb 763.74.8 HMW-MAA binding anti-anti-id Mabs elicited with mAb MK2-23 were characterized in their reactivity with a large panel of surgically removed benign and malignant melanocytic tumors. The 8 anti-anti-id mAbs displayd subtle differences in their immunoperoxidase staining of both benign and malignant tumors. The diversity in the fine specificity of the 8 anti-anti-id mAbs is likely to reflect the few somatic mutations which occur in the amino-acid sequence of the variable regions of their heavy and light chains in the course of the immune response to mAb MK2-23. The reactivity patterns of the 8 anti-anti-id mAbs with the tissue substrates are similar, although not superimposable upon that of the anti-HMW-MAA mAb 763.74 elicited with melanoma cells. This defference may reflect the imperfect mimicry by anti-id mA … More b MK2-23 of the antigenic determinant defined by anti-HMW-MAA mAb 763.74.Moreover the amino-acid sequences of 8 anti-anti-id mAbs were compared with that of anti-HMW-MAA mAb 763.74.80-95% and 85-100% homology were seen in the amino-acid sequence of the variable regions of their heavy and light chains, respectively. The highest homology was found in CDR1 and lowest in CDR3.(2) Production of anti-melanoma antibodies with anti-Id mAbAdministration of anti-Id mAb elicites anti-anti-Id mAb reacting with human melanoma cells. For the improvement of this efficacy, administration with adjuvant of anti-Id mAb MK2-23 conjugated to a carrier induces more efficiently to anti-anti-Id antibodies reacting with human melanoma cells. Moreover, F (ab') 2 fragment and chimeric mAb MK2-23 were found to reduce the anti-mouse antibodies in rabbit, which may cause the unfaborable side effect.(3) Mechanism of loss of HLA class I in melanoma lesionsThe aim of this study was to investigate the expression of HLA Class 1 antigens in surgically removed melanoma lesions. To this end 32 primary and 11 metastatic lesions were stained in the immunoperoxidase reaction with monoclonal antibodies (mAb) to monomorphic, locus specific and polymorphic antigenic determinants. The intensity of staining of melanoma cells was compared to that of keratinocytes surrounding the tumor nest. The patients' HLA phenotype was determined utilizing the conventional lymphocytotoxicity assay. About 20% of primary and about 50% of metastatic lesions were not stained or were stained with reduced intensity by mAb to monomorphic and locus specific antigenic determinants. Moreover about 40% of primary and about 60% of metastatic lesions were not stained or were stained with low intensity, by mAb to HLA Class 1 allospecificities. These results indicate that the frequency of abnormalities in HLA Class 1 antigen expression is high in melanoma lesions. These abnormalities are likely to have a negative impact on T cell based immunotherapy, since they provide melanoma cells with a mechanism to escape from destruction by cytotoxic T cells. Less

（1）Melanomathe-ID MAB MK2-23中网络的免疫组织化学分析具有抗HMW-MAB 763.74.8 HMW-MAA抗原DEF的内部图像它们与大型外科手术的反应性去除了良性和恶性肿瘤。在对MAB MK2-23的免疫反应过程中，体重链的可变区域的氨基酸序列发生。抗HMW-MAB 763.74引起的H黑色素瘤细胞可能反映出抗ID MA的不完善的模仿...抗HMW-MAB 763.74的抗原型的更多B MK2-23。与抗HMW-MAB 763.74.80-95％和85 -100％同源性的酸序列进行了8种抗抗IDAB的酸序列，在其重和轻链的可变区域中，同源性在CDR1和同源性中均在CDR1和最低的CDR3。发现23个可以减少BBIT中的抗体，这可能会导致不可固定的副作用（3）HLA II级在黑色素瘤中的HLA 1级抗原的效果。在单克隆抗体（MAB）中，使用传统的淋巴细胞毒性含量约有20％的TIC，在免疫过氧化物酶的重新交流中呈现。或用mAb对单态抗原的确定降低，转移性病变的0％的抗原损伤均未染色或低强度结果染色表明HLA 1类抗原表达的频率是对T细胞的负面影响。，因为它们为黑色素瘤细胞提供了一种机制，以逃避细胞毒性T细胞破坏的损害。