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重组痘苗白细胞介素-2感染的肿瘤细胞疫苗在小鼠结肠腺癌免疫治疗中的应用

Recombinant vaccinia interleukin-2-infected tumor cell vaccines in immunotherapy of murine colon adenocarcinoma.

作者信息

Bash J A

机构信息

Department of Medical Laboratory Sciences, Florida International University, Miami 33199.

出版信息

J Immunother Emphasis Tumor Immunol. 1993 Nov;14(4):269-72. doi: 10.1097/00002371-199311000-00003.

Abstract

A recombinant vaccinia virus (vCF13) containing and expressing the gene for human interleukin (IL)-2(vCF13) was compared to a recombinant vaccinia transfection control strain containing the LacZ gene at the same insertion site (vTFCLZ-1) for their ability to augment the immunogenicity of murine colon adenocarcinoma cell lines CT26 and CA51 in Balb/c mice. Both recombinant vaccinia strains abolished tumorigenicity of 10(5) CT26 or CA51 tumor cells. vCF13-infected tumor cells that secreted human IL-2 as measured by both CTLL-2 and enzyme-linked immunosorbent assays induced delay in tumorigenesis when administered in two weekly subcutaneous injections 1 week prior to challenge with 10(5) uninfected tumor cells. Although three of five vCF13-CT26 immunized mice developed tumors by day 14 after challenge, intralesional injection of these tumors with vCF13 induced rapid regression, whereas all five tumors that developed in vTFCLZ-1 immunized mice showed no response to intralesional vTFCLZ-1. These preliminary results provide support for the potential utility of recombinant vaccinia/IL-2 in tumor immunotherapy.

摘要

将含有并表达人白细胞介素(IL)-2基因的重组痘苗病毒(vCF13)与在相同插入位点含有LacZ基因的重组痘苗转染对照株(vTFCLZ-1)进行比较,以研究它们增强Balb/c小鼠体内鼠结肠腺癌细胞系CT26和CA51免疫原性的能力。两种重组痘苗病毒株均消除了10⁵个CT26或CA51肿瘤细胞的致瘤性。通过CTLL-2和酶联免疫吸附测定法检测发现,vCF13感染的肿瘤细胞分泌人IL-2,在以10⁵个未感染肿瘤细胞进行攻击前1周,每周两次皮下注射这种细胞可诱导肿瘤发生延迟。尽管在攻击后第14天,五分之三的vCF13-CT26免疫小鼠出现了肿瘤,但瘤内注射vCF13可使这些肿瘤迅速消退,而vTFCLZ-1免疫小鼠中出现的所有五个肿瘤对瘤内注射vTFCLZ-1均无反应。这些初步结果为重组痘苗病毒/IL-2在肿瘤免疫治疗中的潜在应用提供了支持。

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