通过将单链抗体整合到包膜中来靶向黑色素瘤细胞的逆转录病毒载体。

Retroviral vector targeting to melanoma cells by single-chain antibody incorporation in envelope.

作者信息

Martin F, Kupsch J, Takeuchi Y, Russell S, Cosset F L, Collins M

机构信息

CRC Center for Cell and Molecular Biology, Institute of Cancer Research, Chester Beatty Laboratories, London, UK.

出版信息

Hum Gene Ther. 1998 Mar 20;9(5):737-46. doi: 10.1089/hum.1998.9.5-737.

DOI:10.1089/hum.1998.9.5-737

PMID:9551621

Abstract

Two strategies for targeting recombinant retroviruses to melanoma cells were compared. One was to extend the tropism of an ecotropic envelope to human melanoma cells, the other was to enhance the tropism of an amphotropic envelope for melanoma cells. Chimeric retroviral envelopes, incorporating a single-chain antibody (ScFv) directed against high-molecular-weight melanoma-associated antigen (HMWMAA) at the amino terminus are correctly processed and incorporated into virions. ScFv-ecotropic envelope chimeras allow specific, but low-titer, targeting of HMWMAA-positive cells, when co-expressed with ecotropic envelopes. ScFv-amphotropic envelope chimeras bind specifically to HMWMAA-positive cells and allow preferential infection at high titer.

摘要

比较了两种将重组逆转录病毒靶向黑色素瘤细胞的策略。一种是将亲嗜性包膜的嗜性扩展至人黑色素瘤细胞，另一种是增强双嗜性包膜对黑色素瘤细胞的嗜性。在氨基末端掺入针对高分子量黑色素瘤相关抗原（HMWMAA）的单链抗体（ScFv）的嵌合逆转录病毒包膜能够被正确加工并整合到病毒颗粒中。当与亲嗜性包膜共表达时，ScFv-亲嗜性包膜嵌合体可实现对HMWMAA阳性细胞的特异性但低滴度靶向。ScFv-双嗜性包膜嵌合体可特异性结合HMWMAA阳性细胞，并允许高滴度的优先感染。