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体外衍生的原发性黑素瘤细胞:免疫治疗疫苗的意义。

Ex vivo derived primary melanoma cells: implications for immunotherapeutic vaccines.

机构信息

1. Department of Microbiology and Immunology, New York Medical College, Valhalla, New York, 10595;

出版信息

J Cancer. 2013 Jun 19;4(5):371-82. doi: 10.7150/jca.6625. Print 2013.

DOI:10.7150/jca.6625
PMID:23833682
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3701807/
Abstract

Transformation of the pigment producing melanocytes into melanoma is a complex multi-step process involving the enhanced expression of various antigens considered as immunotherapeutic targets. Significant progress in melanoma research has been made over the years and has resulted in the identification of various antigens over expressed in melanoma as well as advances in immunotherapeutic treatments, which focus on modulating the immune systems response to melanoma. Despite these advances, incidences of melanoma are still on the rise thus warranting additional research in identifying new therapeutic treatments. Our focus is on developing a multivalent immunotherapeutic vaccine that targets various melanoma associated antigens. The approach focuses on the use of five primary patient derived melanoma cells (MEL-2, MEL-V, 3MM, KFM, and GLM-2, which have been characterized in this study. These cells express differential amounts of various melanoma associated antigens such as MART-1, gp100 (Pmel17), MAGE-A1 and tyrosinase as well a cell surface antigens essential for melanoma cell metastasis, such as CD146 and CD71. In addition these cells display differential in vitro migratory and invasive properties as well as have the ability to form solid tumors when implanted into BALB/c nude mice. The retention of the innate phenotype of these primary patient derived cells together with the expression of a multitude repertoire of melanoma associated antigens offers a novel opportunity to target melanoma so as to avoid immune evasion.

摘要

黑色素细胞向黑色素瘤的转化是一个复杂的多步骤过程,涉及到各种被认为是免疫治疗靶点的抗原的增强表达。近年来,黑色素瘤的研究取得了重大进展,鉴定出了多种在黑色素瘤中过度表达的抗原,并在免疫治疗方面取得了进展,这些进展集中在调节免疫系统对黑色素瘤的反应上。尽管取得了这些进展,但黑色素瘤的发病率仍在上升,因此需要进一步研究以确定新的治疗方法。我们的重点是开发一种针对多种黑色素瘤相关抗原的多价免疫治疗疫苗。该方法侧重于使用五种源自患者的黑色素瘤细胞(MEL-2、MEL-V、3MM、KFM 和 GLM-2),这些细胞在本研究中已得到表征。这些细胞表达不同量的各种黑色素瘤相关抗原,如 MART-1、gp100(Pmel17)、MAGE-A1 和酪氨酸酶,以及黑色素瘤细胞转移所必需的细胞表面抗原,如 CD146 和 CD71。此外,这些细胞表现出不同的体外迁移和侵袭特性,并且当植入 BALB/c 裸鼠时能够形成实体瘤。这些源自患者的原始细胞保持固有表型,同时表达多种黑色素瘤相关抗原,为靶向黑色素瘤提供了一个新的机会,以避免免疫逃逸。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aae1/3701807/228ef71f75b9/jcav04p0371g07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aae1/3701807/4a216813ed36/jcav04p0371g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aae1/3701807/b6190bbd4472/jcav04p0371g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aae1/3701807/7493e14ea852/jcav04p0371g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aae1/3701807/9f1a0e335a0c/jcav04p0371g06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aae1/3701807/228ef71f75b9/jcav04p0371g07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aae1/3701807/4a216813ed36/jcav04p0371g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aae1/3701807/b6190bbd4472/jcav04p0371g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aae1/3701807/7493e14ea852/jcav04p0371g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aae1/3701807/9f1a0e335a0c/jcav04p0371g06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aae1/3701807/228ef71f75b9/jcav04p0371g07.jpg

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