• 1.解放軍第451醫(yī)院肝膽普外科(陜西西安 710054);;
  • 2.解放軍第451醫(yī)院特診科(陜西西安 710054);;
  • 3.第四軍醫(yī)大學(xué)西京醫(yī)院消化病研究所(陜西西安 710032);;
  • 4.第四軍醫(yī)大學(xué)西京醫(yī)院肝膽外科(陜西西安 710032);

目的  制備腫瘤相關(guān)糖蛋白-72抗原(TAG-72)嵌合錨定T細(xì)胞,通過(guò)體外實(shí)驗(yàn)檢測(cè)其對(duì)乳腺癌細(xì)胞的抑癌活性。
方法  分離健康人外周血單個(gè)核細(xì)胞(PBMC),采用脂質(zhì)體lipofectamineTM 2000介導(dǎo)的細(xì)胞瞬時(shí)轉(zhuǎn)染方法,將已制備的重組真核表達(dá)載體即抗TAG-72-scFv-CD3ζ-pcDNA 3.0導(dǎo)入PBMC,以獲得TAG-72嵌合錨定T細(xì)胞,以此為轉(zhuǎn)染組;用轉(zhuǎn)染空載體pcDNA 3.0的PBMC作為對(duì)照組。將轉(zhuǎn)染組嵌合錨定T細(xì)胞和對(duì)照組PBMC細(xì)胞分別與乳腺癌細(xì)胞系MCF-7及Bcap37共培養(yǎng),觀察兩者對(duì)乳腺癌細(xì)胞G1期的阻滯率。
結(jié)果  轉(zhuǎn)染組對(duì)MCF-7細(xì)胞系的G1期阻滯率為(82.3±6.9)%,對(duì)照組為(43.4±3.9)%,2組間比較差異具有統(tǒng)計(jì)學(xué)意義(P<0.05);轉(zhuǎn)染組對(duì)Bcap37細(xì)胞系的G1期阻滯率為(51.3±4.7)%,對(duì)照組為(45.6±2.5)%,2組間比較差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05)。
結(jié)論  TAG-72嵌合錨定T細(xì)胞可特異性地抑制TAG-72+乳腺癌細(xì)胞的增殖,此將為乳腺癌的臨床診治提供一種有希望的途徑。

引用本文: 徐宏勇,丁蓉,徐立,李開(kāi)宗. TAG-72嵌合錨定T細(xì)胞對(duì)乳腺癌的抑癌效應(yīng)觀察△. 中國(guó)普外基礎(chǔ)與臨床雜志, 2012, 19(12): 1298-1301. doi: 復(fù)制

1. June CH, Bluestone JA, Nadler LM, et al. The B7 and CD28 receptor families[J]. Immunol Today, 1994, 15(7): 321-331.
2. Kapsogeorgou EK, Moutsopoulos HM, Manoussakis MN. Functional expression of a costimulatory B7.2 (CD86) protein on human salivary gland epithelial cells that interacts with the CD28 receptor, but has reduced binding to CTLA4[J]. J Immunol, 2001, 166(5): 3107-3113.
3. 徐立, 徐宏勇, 樊代明. 胃腸道腫瘤靶向抗癌胚抗原單鏈抗體與T細(xì)胞表面受體基因的融合分子構(gòu)建[J]. 中華消化雜志, 2004, 24(2): 75-77.
4. 徐宏勇, 徐立, 李開(kāi)宗, 等. 抗腫瘤相關(guān)糖蛋白-72單抗在人乳腺癌中的表達(dá)[J]. 中國(guó)普外基礎(chǔ)與臨床雜志, 2006, 13(5): 540-541.
5. Hombach A, Heuser C, Marquardt T, et al. CD4+ T cells engra-fted with a recombinant immunoreceptor efficiently lyse target cells in a MHC antigen- and Fas-independent fashion[J]. JImmunol, 2001, 167(2): 1090-1096.
6. Hombach AA, Schildgen V, Heuser C, et al. T cell activation by antibody-like immunoreceptors: the position of the binding epitope within the target molecule determines the efficiency of activation of redirected T cells[J]. J Immunol, 2007, 178(7): 4650-4657.
7. 徐宏勇, 徐立, 高建宏, 等. 嵌合錨定T細(xì)胞致癌胚抗原陽(yáng)性胃癌細(xì)胞的凋亡效應(yīng)[J]. 中華醫(yī)學(xué)雜志, 2007, 87(15): 1053-1057.
8. 徐宏勇, 徐立, 李開(kāi)宗, 等. 嵌合錨定融合分子在T淋巴細(xì)胞的熒光表達(dá)及檢測(cè)[J]. 中國(guó)普外基礎(chǔ)與臨床雜志, 2010, 17(10): 1046-1049.
9. 徐宏勇, 徐立, 李開(kāi)宗, 等. 癌胚抗原嵌合錨定T細(xì)胞對(duì)胃癌的體內(nèi)外抑癌效應(yīng)觀察[J]. 中華外科雜志, 2008, 46(2): 148-149.
10. Ychou M, Duffour J, Kramar A, et al. Clinical significance and prognostic value of CA72-4 compared with CEA and CA19-9 in patients with gastric cancer[J]. Dis Markers, 2000, 16(3-4): 105-110.
11. Wang XB, Zhao BF, Zhao Q, et al. A new recombinant single chain trispecific antibody recruits T lymphocytes to kill CEA (carcinoma embryonic antigen) positive tumor cells in vitroefficiently[J]. J Biochem, 2004, 135(4): 555-565.
12. Petersen CC, Petersen MS, Agger R, et al. Accumulation in tumor tissue of adoptively transferred T cells:a comparison between intravenous and intraperitoneal injection[J]. J Immunother, 2006, 29(3): 241-249.
13. Takizawa K, Kitani S, Takeuchi F, et al. Enhanced expression of CD69 and CD25 antigen on human peripheral blood mononuclear cells by prolactin[J]. Endocr J, 2005, 52(5): 635-641.
  1. 1. June CH, Bluestone JA, Nadler LM, et al. The B7 and CD28 receptor families[J]. Immunol Today, 1994, 15(7): 321-331.
  2. 2. Kapsogeorgou EK, Moutsopoulos HM, Manoussakis MN. Functional expression of a costimulatory B7.2 (CD86) protein on human salivary gland epithelial cells that interacts with the CD28 receptor, but has reduced binding to CTLA4[J]. J Immunol, 2001, 166(5): 3107-3113.
  3. 3. 徐立, 徐宏勇, 樊代明. 胃腸道腫瘤靶向抗癌胚抗原單鏈抗體與T細(xì)胞表面受體基因的融合分子構(gòu)建[J]. 中華消化雜志, 2004, 24(2): 75-77.
  4. 4. 徐宏勇, 徐立, 李開(kāi)宗, 等. 抗腫瘤相關(guān)糖蛋白-72單抗在人乳腺癌中的表達(dá)[J]. 中國(guó)普外基礎(chǔ)與臨床雜志, 2006, 13(5): 540-541.
  5. 5. Hombach A, Heuser C, Marquardt T, et al. CD4+ T cells engra-fted with a recombinant immunoreceptor efficiently lyse target cells in a MHC antigen- and Fas-independent fashion[J]. JImmunol, 2001, 167(2): 1090-1096.
  6. 6. Hombach AA, Schildgen V, Heuser C, et al. T cell activation by antibody-like immunoreceptors: the position of the binding epitope within the target molecule determines the efficiency of activation of redirected T cells[J]. J Immunol, 2007, 178(7): 4650-4657.
  7. 7. 徐宏勇, 徐立, 高建宏, 等. 嵌合錨定T細(xì)胞致癌胚抗原陽(yáng)性胃癌細(xì)胞的凋亡效應(yīng)[J]. 中華醫(yī)學(xué)雜志, 2007, 87(15): 1053-1057.
  8. 8. 徐宏勇, 徐立, 李開(kāi)宗, 等. 嵌合錨定融合分子在T淋巴細(xì)胞的熒光表達(dá)及檢測(cè)[J]. 中國(guó)普外基礎(chǔ)與臨床雜志, 2010, 17(10): 1046-1049.
  9. 9. 徐宏勇, 徐立, 李開(kāi)宗, 等. 癌胚抗原嵌合錨定T細(xì)胞對(duì)胃癌的體內(nèi)外抑癌效應(yīng)觀察[J]. 中華外科雜志, 2008, 46(2): 148-149.
  10. 10. Ychou M, Duffour J, Kramar A, et al. Clinical significance and prognostic value of CA72-4 compared with CEA and CA19-9 in patients with gastric cancer[J]. Dis Markers, 2000, 16(3-4): 105-110.
  11. 11. Wang XB, Zhao BF, Zhao Q, et al. A new recombinant single chain trispecific antibody recruits T lymphocytes to kill CEA (carcinoma embryonic antigen) positive tumor cells in vitroefficiently[J]. J Biochem, 2004, 135(4): 555-565.
  12. 12. Petersen CC, Petersen MS, Agger R, et al. Accumulation in tumor tissue of adoptively transferred T cells:a comparison between intravenous and intraperitoneal injection[J]. J Immunother, 2006, 29(3): 241-249.
  13. 13. Takizawa K, Kitani S, Takeuchi F, et al. Enhanced expression of CD69 and CD25 antigen on human peripheral blood mononuclear cells by prolactin[J]. Endocr J, 2005, 52(5): 635-641.