Paper Infomation
The Progress in Immunoproapoptotin Molecules Targeting Tumor Cells
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Author: Tao Wang, Junlin Ren, Lintao Jia, Angang Yang
Abstract: Immunoproapoptotin consists of a single-chain antibody against tumor-specific surface marker and an active domain which has the function of translocation and pro-apoptosis. This fused recombinant protein can specifically recognize and kill tumor cells. Immunoproapoptotin comes from immunotoxin which is proved not successful in clinical trials by inducing neutralizing antibody and other side effects due to the heterogenous toxins domains from bacteria or plants. To avoid the immunogenicity of immunotoxin, effectors from human were employed in the 2nd generation of Immunoproapoptotin. However, the translocation domain is still heterogenous and the efficiency of translocation is limited. In the latest progress, a furin cleavage site was used to substitute for the translocation domain and thus enhanced the translocation efficiency and greatly reduced the immunogenicity of Immunoproapoptotin, demonstrating a wide clinical application prospects.
Keywords: Tumor; Target Killing; Immunoproapoptotin Molecule
References:
[1] Madhumathi J, Verma RS. Therapeutic targets and recent advances in protein immunotoxins. Curr Opin Microbiol. 2012 Jun; 15(3): 300-9
[2] Kounnas MZ, Morris RE, Thompson MR, FitzGerald DJ, Strickland DK, Saelinger CB. The alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein binds and internalizes Pseudomonas exotoxin A. J Biol Chem. 1992 Jun 25; 267(18): 12420-3
[3] Adkins I, Holubova J, Kosova M, Sadilkova L. Bacteria and their toxins tamed for immunotherapy. Curr Pharm Biotechnol. 2012 Jun; 13(8): 1446-73
[4] Frankel AE, Fleming DR, Hall PD, Powell BL, Black JH, Leftwich C, Gartenhaus R. A phase II study of DT fusion protein denileukindiftitox in patients with fludarabine-refractory chronic lymphocytic leukemia. Clin Cancer Res. 2003 Sep 1; 9(10 Pt 1): 3555-61
[5] Chen SY, Yang AG, Chen JD, Kute T, King CR, Collier J, Cong Y, Yao C, Huang XF. Potent antitumour activity of a new class of tumour-specific killer cells. Nature. 1997 Jan 2; 385(6611): 78-80
[6] Litvak-Greenfeld D, Benhar I. Risks and untoward toxicities of antibody-based immunoconjugates. Adv Drug Deliv Rev. 2012 Dec; 64(15): 1782-99
[7] Govindan SV, Goldenberg DM. Designing immunoconjugates for cancer therapy. Expert Opin Biol Ther. 2012 Jul; 12(7): 873-90
[8] Jia LT, Zhang LH, Yu CJ, Zhao J, Xu YM, Gui JH, Jin M, Ji ZL, Wen WH, Wang CJ, Chen SY, Yang AG. Specific tumoricidal activity of a secreted proapoptotic protein consisting of HER2 antibody and constitutively active caspase-3. Cancer Res. 2003 Jun 15; 63(12): 3257-62
[9] Zhao J, Zhang LH, Jia LT, Zhang L, Xu YM, Wang Z, Yu CJ, Peng WD, Wen WH, Wang CJ, Chen SY, Yang AG. Secreted antibody/granzyme B fusion protein stimulates selective killing of HER2-overexpressing tumor cells. J Biol Chem. 2004 May 14; 279(20): 21343-8
[10] Xu YM, Wang LF, Jia LT, Qiu XC, Zhao J, Yu CJ, Zhang R, Zhu F, Wang CJ, Jin BQ, Chen SY, Yang AG. A caspase-6 and anti-human epidermal growth factor receptor-2 (HER2) antibody chimeric molecule suppresses the growth of HER2-overexpressing tumors. J Immunol. 2004 Jul 1; 173(1): 61-7
[11] Yu CJ, Jia LT, Meng YL, Zhao J, Zhang Y, Qiu XC, Xu YM, Wen WH, Yao LB, Fan DM, Jin BQ, Chen SY, Yang AG. Selective proapoptotic activity of a secreted recombinant antibody/AIF fusion protein in carcinomas overexpressing HER2. Gene Ther. 2006 Feb; 13(4): 313-20
[12] Qiu XC, Xu YM, Wang F, Fan QY, Wang LF, Ma BA, Jia LT, Zhao J, Meng YL, Yao LB, Chen SY, Yang AG. Single-chain antibody/activated BID chimeric protein effectively suppresses HER2-positive tumor growth. Mol Cancer Ther. 2008 Jul; 7(7): 1890-9
[13] Erickson HA, Jund MD, Pennell CA. Cytotoxicity of human RNase-based immunotoxins requires cytosolic access and resistance to ribonuclease inhibition. Protein Eng Des Sel 2006; 19: 37-45
[14] DalkenB, Giesubel U, Knauer SK, Wels WS. Targeted induction of apoptosis by chimeric granzyme B fusion proteins carrying antibody and growth factordomains for cell recognition. Cell Death Differ. 2006; 13: 576-585
[15] Zhang L, Zhao J, Wang T, Yu CJ, Jia LT, Duan YY, Yao LB, Chen SY, Yang AG. HER2-targeting recombinant protein with truncated pseudomonas exotoxin A translocation domain efficiently kills breast cancer cells. Cancer Biol Ther. 2008 Aug; 7(8): 1226-31
[16] Seidah NG. The proproteinconvertases, 20 years later. Methods Mol Biol. 2011; 768: 23-57
[17] Seidah NG. What lies ahead for the proproteinconvertases? Ann N Y Acad Sci. 2011 Mar; 1220: 149-61
[18] Thomas G. Furin at the cutting edge: from protein traffic to embryogenesis and disease. Nat Rev Mol Cell Biol. 2002; 3(10): 753-766
[19] Wang T, Zhao J, Ren JL, Zhang L, Wen WH, Zhang R, Qin WW, Jia LT, Yao LB, Zhang YQ, Chen SY, Yang AG. Recombinant immunoproapoptotic proteins with furin site can translocate and kill HER2-positive cancer cells. Cancer Res. 2007 Dec 15; 67(24): 11830-9
[20] Ren JL, Meng YL, Hu B, Jia LT, Zhang R, Xu YM, Xie QS, Zhang YQ, Jin BQ, Chen SY, Wang T, Yang AG. The effect of direct translocation across endosomes on the cytotoxicity of the recombinant protein e23sFv-Fdt-casp6 to HER2 positive gastric cancer cells. Biomaterials. 2011 Oct; 32(30): 7641-50
[21] Wang F, Ren J, Qiu XC, Wang LF, Zhu Q, Zhang YQ, Huan Y, Meng YL, Yao LB, Chen SY, Xu YM, Yang AG. Selective cytotoxicity to HER2-positive tumor cells by a recombinant e23sFv-TD-tBID protein containing a furin cleavage sequence. Clin Cancer Res. 2010 Apr 15; 16(8): 2284-94
[22] Mahmud H, DälkenB,and Wels W.S. Induction of programmed cell death in ErbB2/HER2-expressingcancer cells by targeted delivery of apoptosis-inducing factor. Mol Cancer Ther. 2009; 8(6): 1526-1535
[23] Cao Y, Marks JD, Marks JW, Cheung LH, Kim S, Rosenblum MG. Construction and characterization of novel, recombinant immunotoxins targeting the Her2/neu oncogene product: in vitro and in vivo studies. Cancer Res. 2009 Dec 1; 69(23): 8987-95