Kantor J, Irvine K, Abrams S, Kaufman H, DiPietro J, Schlom J
Laboratory of Tumor Immunology and Biology, National Cancer Institute, Bethesda, Md 20892.
J Natl Cancer Inst. 1992 Jul 15;84(14):1084-91. doi: 10.1093/jnci/84.14.1084.
Human carcinoembryonic antigen (CEA) is a 180-kd glycoprotein expressed in human colorectal, gastric, pancreatic, breast, and non-small-cell lung carcinomas. Previous studies have demonstrated enhanced immune responses to other antigens presented with vaccinia virus proteins via a recombinant vaccinia virus construct. In addition, we have developed a recombinant CEA-vaccinia virus construct, designated rV(WR)-CEA, and have demonstrated humoral anti-CEA responses in mice after immunization with that virus.
The goals of this study were (a) to construct a recombinant CEA-vaccinia vaccine in a less virulent vaccinia strain that is potentially safe and effective for treatment of patients whose tumors express CEA and (b) to evaluate the ability of the recombinant CEA-vaccinia vaccine to prevent and reverse tumor growth in mice and to elicit cell-mediated and humoral anti-CEA immune responses.
Using the New York City strain of vaccinia virus, which is used in smallpox vaccination and is more attenuated for humans than rV(WR), we derived a recombinant CEA-vaccinia construct, designated rV(NYC)-CEA. The ability of this construct to induce antitumor immunity was evaluated in mice receiving subcutaneous injections of murine colon adenocarcinoma cells expressing the human CEA gene.
Administration of rV(NYC)-CEA in mice induced strong anti-CEA antibody responses, as well as CEA-specific cell-mediated responses, including delayed-type hypersensitivity, lymphoproliferative, and cytotoxic responses. Vaccination of mice with the rV(NYC)-CEA rendered them resistant to the growth of subsequently transplanted CEA-expressing tumors. Moreover, when mice were vaccinated 7 days after tumor cell injection, tumor growth was either greatly reduced or eliminated. No toxic effects were observed in any of the mice.
These studies demonstrate that antitumor activity can be induced with the use of a recombinant CEA-vaccinia virus construct derived from an attenuated vaccinia strain, and they reveal the range of cell-mediated and humoral responses induced by this recombinant vaccine.
人癌胚抗原（CEA）是一种180kd的糖蛋白，在人类结直肠癌、胃癌、胰腺癌、乳腺癌和非小细胞肺癌中表达。先前的研究表明，通过重组痘苗病毒构建体，对与痘苗病毒蛋白呈递的其他抗原的免疫反应增强。此外，我们已经开发出一种重组CEA - 痘苗病毒构建体，命名为rV(WR)-CEA，并已证明用该病毒免疫小鼠后会产生体液抗CEA反应。
本研究的目标是（a）在一种毒性较低的痘苗病毒株中构建重组CEA - 痘苗疫苗，该疫苗对肿瘤表达CEA的患者可能安全有效，以及（b）评估重组CEA - 痘苗疫苗预防和逆转小鼠肿瘤生长以及引发细胞介导和体液抗CEA免疫反应的能力。
使用用于天花疫苗接种且对人类比rV(WR)更减毒的纽约市痘苗病毒株，我们获得了一种重组CEA - 痘苗构建体，命名为rV(NYC)-CEA。在皮下注射表达人CEA基因的小鼠结肠腺癌细胞的小鼠中评估该构建体诱导抗肿瘤免疫的能力。
给小鼠施用rV(NYC)-CEA可诱导强烈的抗CEA抗体反应以及CEA特异性细胞介导反应，包括迟发型超敏反应、淋巴细胞增殖反应和细胞毒性反应。用rV(NYC)-CEA对小鼠进行疫苗接种使其对随后移植的表达CEA的肿瘤生长具有抗性。此外，当在肿瘤细胞注射7天后给小鼠接种疫苗时，肿瘤生长要么大大减少要么消除。在任何小鼠中均未观察到毒性作用。
这些研究表明，使用源自减毒痘苗病毒株的重组CEA - 痘苗病毒构建体可诱导抗肿瘤活性，并揭示了这种重组疫苗诱导的细胞介导和体液反应范围。
