生物谷： 碳酸酐酶IX (carbonic anhydrase IX,，CA9)是腎細(xì)胞癌(Renal Cell Carcinoma,，RCC)特異細(xì)胞膜蛋白,，與RCC的致死性有關(guān)，在80％的原發(fā)性,、轉(zhuǎn)移性特別是常見的透明細(xì)胞型（common clear cell variant）RCC中都有表達(dá),。熱休克蛋白（Heat shock proteins ，HSP's）結(jié)合和保護(hù)部分變性蛋白,，有時會用于發(fā)展疫苗。疫苗Oncophage（vitespen）是一種將HSP's作為提呈腫瘤特異抗原平臺的策略,。Roswell Park癌癥研究所Hyung L.Kim與其同事在其臨床前研究中利用RENCA模型,，檢測HSP 110:CA9疫苗配方治療RCC的效果。
研究人員在表達(dá)CA9的遺傳工程小鼠體內(nèi),，利用RCC的RENCA模型,，檢測3種CA9 DNA疫苗配方（formulations）：①全長CA9＋hsp110②一段CA9＋hsp110③CA9＋HSP grp170的療效。實(shí)驗(yàn)過程中,，研究人員首先用3種疫苗配方免疫小鼠,，然后注射腫瘤細(xì)胞，監(jiān)控小鼠腫瘤生長情況（效仿佐劑治療模型）,。第①種配方免疫的小鼠40天內(nèi)沒有腫瘤生長,，體內(nèi)有抗CA9抗體，Elispot檢測中出現(xiàn)CA-9特異性IFNγ反應(yīng),；第②種配方免疫的小鼠抑制但不能阻止腫瘤生長,，第③種配方?jīng)]有抗腫瘤效果。另一組實(shí)驗(yàn)中,，研究人員為已經(jīng)出現(xiàn)RENCA腫瘤的小鼠注射全長CA9：hsp110,，結(jié)果與對照組相比，實(shí)驗(yàn)組小鼠的腫瘤生長得到抑制（p＝0.0001）,，但腫瘤沒有衰退,。
CA9是一種RCC特異性分子靶標(biāo)，已經(jīng)應(yīng)用于多種RCC治療策略中,，包括抗體策略和最近的以這些分子為靶標(biāo)的疫苗策略,。此次臨床前研究結(jié)果說明全長CA9+hsp110的疫苗也許是臨床研究中靶向CA9的有效策略，不足之處是研究所用模型不能檢測表達(dá)CA9的正常組織（如膽管上皮）反應(yīng)中出現(xiàn)毒性的可能,，這些毒性會阻礙此策略的臨床發(fā)展,。（引自生物通）
原始出處：
Cancer Immunology, Immunotherapy，Volume 56, Number 7 / 2007年7月
Evaluation of renal cell carcinoma vaccines targeting carbonic anhydrase IX using heat shock protein 110
Hyung L. Kim1 , Xiaolei Sun1, John R. Subjeck2 and Xiang-Yang Wang1, 2
(1) Department of Urologic Oncology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA
(2) Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY, USA
Received: 3 October 2006 Accepted: 10 November 2006 Published online: 5 December 2006
Abstract Carbonic anhydrase IX (CA9) is a renal cell carcinoma (RCC)-specific tumor protein that is targeted using heat shock protein 110 (hsp110). The chaperoning ability of hsp110 can be utilized to form a complex with CA9 (hsp110 + CA9) in vitro, which can be administered as a highly concentrated tumor vaccine. In a tumor prevention model, hsp110 + CA9 prevented the growth of RENCA tumors in BALB/c mice, and produced IFN-γ response measured using ELISPOT and an antibody response measured using ELISA. To test a second vaccine strategy, hsp110 complexed to a previously described CA9 peptide prevented tumor growth and produced a very weak IFN-γ response, but no antibody response. A plasmid vector containing grp170, a member of the hsp110 family, linked to CA9 did not produce an antitumor response and produced no IFN-γ response or antibodies. In a model of metastatic RCC, RENCA cells were injected intradermally prior to vaccination. Hsp110 + CA9 decreased tumor growth compared to control vaccinations. These studies suggest that recombinant hsp110 complexed to CA9 should be evaluated for treatment of RCC.
Keywords Renal cell carcinoma - Carbonic anhydrase IX - Heat shock protein - Tumor vaccine - RENCA - Heat shock protein 110
