间皮素与肿瘤靶向治疗
摘要
<正>间皮素(mesothelin,MSLN)是一种细胞表面糖蛋白,在正常组织中很少表达,但在卵巢癌、胰腺癌和恶性间皮瘤等肿瘤组织中高表达~([1]),因此间皮素有望成为癌症治疗的重要靶点。由于间皮素基因敲除小鼠未发现表型异常,所以间皮素的生物学功能目前仍不清楚,但有研究表明间皮素可能在肿瘤细胞增殖、黏附及耐药性方面起着重要作用。采用抗
引文
[1]Baldo P,Cecco S.Amatuximab and novel agents targeting mesothelin for solid tumors.Onco Targets Ther,2017,10:5337-5353.
[2]Pastan I,Hassan R.Discovery of mosothelin and exploiting it as a target for immunotherapy.J Cancer Res,2014,74(11):2907-2912.
[3]Manzanares Má,Campbell DJW,Maldonado GT,et al.Overexpression of periostin and distinct mesothelin forms predict malignant progression in a rat cholangiocarcinoma model.Hepatol Commun,2018,2(2):155-172.
[4]Burt BM,Lee HS,Lenge De Rosen V,et al.Soluble mesothelin-related peptides to monitor recurrence after resection of pleural mesothelioma.Ann Thorac Surg,2017,104(5):1679-1687.
[5]Asgarov K,Balland J,Tirole C,et al.A new anti-mesothelin antibody targets selectively the membrane-associated form.MAbs,2017,9(3):567-577.
[6]Aguilar-Madrid G,Pesch B,Calderón-Aranda ES,et al.Biomarkers for predicting malignant pleural mesothelioma in a mexican population.Int J Med Sci,2018,15(9):883-891.
[7]Nichetti F,Marra A,Corti F,et al.The role of mesothelin as a diagnostic and therapeutic target in pancreatic ductal adenocarcinoma:a comprehensive review.Target Oncol,2018,13(3):333-351.
[8]Ofek G,McKee K,Yang Y,et al.Relationship between antibody 2F5neutralization of HIV-1 and hydrophobicity of its heavy chain third complementarity-determining region.J Virol,2010,84(6):2955-2962.
[9]Tassev DV,Cheung NK.Monoclonal antibody therapies for solid tumors.Expert Opin Biol Ther,2009,9(3):341-353.
[10]Coelho R,Marcos-Silva L,Ricardo S,et al.Peritoneal dissemination of ovarian cancer:role of MUC16-mesothelin interaction and implications for treatment.Expert Rev Anticancer Ther,2018,18(2):177-186.
[11]Rump A,Morikawa Y,Tanaka M,et al.Binding of ovarian cancer antigen CA125/MLTC16 to mesothelin mediates cell adhesion.J Biol Chem,2004,279(10):9190-9198.
[12]Bharadwaj U,Marin-Muller C,Li M,et al.Mesothelin confers pancreatic cancer cell resistance to TNF-α-induced apoptosis through Akt/PI3K/NF-κB activation and IL-6/Mcl-1 overexpression.Mol Cancer,2011,10:106.
[13]Li M,Bharadwaj U,Zhang R,et al.Mesothelin is a malignant factor and therapeutic vaccine target for pancreatic cancer.Mol Cancer Ther,2008,7(2):286-296.
[14]Bharadwj U,Li M,Chen C,et al.Mesothelin-induced pancreatic cancer cell proliferation involves alteration of cyclin E via activation of signal transducer and activator of transcription protein 3.Mol Cancer Res,2008,6(11):1755-1765.
[15]Cheng WF,Huang CY,Chang MC,et al.High mesothelin correlates with chemoresistance and poor survival in epithelial ovarian carcinoma.J Br Cancer,2009,100(7):1144-1153.
[16]Chang K,Pai LH,Pass H,et al.Monoclonal antibody K1 reacts with epithelial mesothelioma but not lung adenocarcinoma.Am J Surg Pathol,1992,16(3):259-268.
[17]Ordó?ez NG.Application of mesothelin immunostaining in tumor diagnosis.Am J Surg Pathol,2003,27(11):1418-1428.
[18]Argani P,Iacobuzio-Donahue C,Ryu B,et al.Mesothelin is overexpressed in the vast majority of ductal adenocarcinomas of the pancreas:identification of a new pancreatic cancer marker by serial analysis of gene expression(SAGE).Clin Cancer Res,2001,7(12):3862-3868.
[19]Zhu QY,Tu ZX,Li ZS,et al.Expression of mesothelin in pancreatic carcinoma tissue and its clinical significance.Chin J Pancreatology,2005,5(1):17-20.(in Chinese)朱庆云,屠振兴,李兆申,等.Mesothelin在胰腺癌组织的表达及其临床意义.胰腺病学,2005,5(1):17-20.
[20]Chang K,Pastan I.Molecular cloning of mesothelin,a differentiation antigen present on mesothelium,mesotheliomas,and ovarian cancers.Proc Natl Acad Sci U S A,1996,93(1):136-140.
[21]Hanaoka T,Hasegawa K,Kato T,et al.Correlation between tumor mesothelin expression and serum mesothelin in patients with epithelial ovarian carcinoma:a potential noninvasive biomarker for mesothelin-targeted therapy.Mol Diagn Ther,2017,21(2):187-198.
[22]Bayoglu IV,Kucukzeybek BB,Kucukzeybek Y,et al.Prognostic value of mesothelin expression in patients with triple negative and HER2-positive breast cancers.Biomed Pharmacother,2015,70:190-195.
[23]Zhou J,He Y,Zhu Y,et al.Expression and clinical significance of mesothelin in breast cancer.J Clin Oncol,2012,17(11):976-979.(in Chinese)周晶,何烨,朱娅,等.间皮素在乳腺癌中的表达及其临床意义.临床肿瘤学杂志,2012,17(11):976-979.
[24]Miettinen M,Sarlomo-Rikala M.Expression of calretinin,thrombomodulin,keratin 5,and mesothelin in lung carcinomas of different types:an immunohistochemical analysis of 596 tumors in comparison with epithelioid mesotheliomas of the pleura.Am J Surg Pathol,2003,27(2):150-158.
[25]Ho M,Bera TK,Willingham MC,et al.Mesothelin expression in human lung cancer.Clin Cancer Res,2007,13(5):1571-1575.
[26]Baba K,Ishigami S,Arigami T,et al.Mesothelin expression correlates with prolonged patient survival in gastric cancer.J Surg Oncol,2012,105(2):195-199.
[27]Einama T,Homma S,Kamachi H,et al.Luminal membrane expression of mesothelin is a prominent poor prognostic factor for gastric cancer.J Br Cancer,2012,107(1):137-142.
[28]Hassan R,Ebel W,Routh Ier EL,et al.Preclinical evaluation of MORAB-009,a chimeric antibody targeting tumor-associated mesothelin.Cancer Immun,2007,7:20.
[29]Hassan R,Cohen SJ,Phillips M,et al.Phase I clinical trial of the chimeric anti-mesothelin monoclonal antibody MORAb-009 in patients with mesothelin-expressing cancers.Clin Cancer Res,2010,16(24):6132-6138.
[30]Hassan R,Kindler HL,Jahan T,et al.Phase II clinical trial of amatuximab,a chimeric antimesothelin antibody with pemetrexed and cisplatin in advanced unresectable pleural mesothelioma.Clin Cancer Res,2014,20(23):5927-5936.
[31]Nakano T.Systemic treatment of malignant pleural mesothelioma.Gan to Kagaku Ryoho,2017,44(13):2041-2047.
[32]Feng Y,Xiao X,Zhu Z,et al.A novel human monoclonal antibody that binds with high affinity to mesothelin-expressing cells and kills them by antibody-dependent cell-mediated cytotoxicity.Mol Cancer Ther,2009,8(5):1113-1118.
[33]Bendell J,Blumenschein G,Zinner R,et al.Abstract LB-291:First-in-human phase I dose escalation study of a novel anti-mesothelin antibody drug conjugate(ADC),BAY 94-9343,in patients with advanced solid tumors.Cancer Res,2013,73(8 Suppl):291.
[34]Gupta A,Hussein Z,Hassan R,et al.Population pharmacokinetics and exposure-response relationship of amatuximab,an anti-mesothelin monoclonal antibody,in patients with malignant pleural mesothelioma and its application in dose selection.Cancer Chemother Pharmacol,2016,77(4):733-743.
[35]Golfier S,Kopitz C,Kahnert A,et al.Anetumab ratvansine:a novel mesothelin-targeting antibody-drug conjugate cures tumors with heterogeneous target expression favored by bystander effect.Mol Cancer Ther,2014,13(6):1537-1548.
[36]Fujisaka Y,Kurata T,Tanaka K,et al.Phase I study of amatuximab,a novel monoclonal antibody to mesothelin,in Japanese patients with advanced solid tumors.Invest New Drugs,2015,33(2):380-388.
[37]Lindenberg L,Thomas A,Adler S,et al.Safety and biodistribution of111In-amatuximab in patients with mesothelin expressing cancers using Single Photon Emission Computed Tomography-Computed Tomography(SPECT-CT)imaging.Oncotarget,2015,6(6):4496-4504.
[38]Okeley NM,Miyamoto JB,Zhang X,et al.Intracellular activation of SGN 35,a potent anti-CD30 antibody drug conjugate.Clin Cancer Res,2010,16(3):888-897.
[39]Scales SJ,Gupta N,Pacheco G,et al.An antimesothelin-monomethyl auristatine conjugate with potent antitumor activity in ovarian,pancreatic,and mesothelioma models.Mol Cancer Ther,2014,13(11):2630-2640.
[40]Weekes CD,Lamberts LE,Borad MJ,et al.Phase I study of DMOT4039A,an antibody-drug conjugate targeting mesothelin,in patients with unresectable pancreatic or platinum-resistant ovarian cancer.Mol Cancer Ther,2016,15(3):439-447.
[41]Pogue S,Chen X,Alexander S,et al.Fully human antimesothelin antibody drug conjugate demonstrates antitumor effects in human lung cancer models.Clin Cancer Res,2008,14(15 Suppl):A13.
[42]Terrett JA,Pogue SL,Toy K,et al.Human antibodies that bind mesothelin,and uses thereof:US,8399623.2013-03-19.
[43]Nagaya T,Nakamura Y,Sato K,et al.Near infrared photoimmunotherapy with an anti-mesothelin antibody.Oncotarget,2016,7(17):23361-23369.
[44]Bristol-Myers Squibb.A study of BMS-986148 in patients with select advanced solid tumors.2015(2019-04-14)[2019-01-22].https://clinicaltrials.gov/show/NCT02341625.
[45]Kolyvas E,Rudloff M,Poruchynsky M,et al.Mesothelin-targeted immunotoxin RG7787 has synergistic anti-tumor activity when combined with taxanes.Oncotarget,2017,8(6):9189-9199.
[46]Hassan R,Lerner MR,Benbrook D,et al.Antitumor activity of SS(dsFv)PE38 and SS1(dsFv)PE38,recombinant antimesothelin immunotoxins against human gynecologic cancers grown in organotypic culture in vitro.Clin Cancer Res,2002,8(11):3520-3526.
[47]Li Q,Verschraegen CF,Mendoza J,et al.Cytotoxic activity of the recombinant anti-mesothelin immunotoxin,SS1(dsFv)PE38,towards tumor cell lines established from ascites of patients with peritoneal mesotheliomas.Anticancer Res,2004,24(3a):1327-1335.
[48]Hassan R,Bullock S,Premkumar A,et al.Phase I study of SS1P,a recombinant anti-mesothelin immunotoxin given as a bolus I.V.infusion to patients with mesothelin-expressing mesothelioma,ovarian,and pancreatic cancers.Clin Cancer Res,2007,13(17):5144-5149.
[49]Watanabe K,Luo Y,Da T,et al.Pancreatic cancer therapy with combined mesothelin-redirected chimeric antigen receptor T cells and cytokine-armed oncolytic adenoviruses.JCI Insight,2018,3(7):99573.
[50]Lanitis E,Poussin M,Hagemann IS,et al.Redirected antitumor activity of primary human lymphocytes transduced with a fully human anti-mesothelin chimeric receptor.Mol Ther,2012,20(3):633-643.
[51]Beatty GL,Haas AR,Maus MV,et al.Mesothelin-specific chimeric antigen receptor mRNA-engineered T cells induce anti-tumor activity in solid malignancies.Cancer Immunol Res,2014,2(2):112-120.
[52]Adusumilli PS,Cherkassky L,Villena-Vargas J,et al.Regional delivery of mesothelin-targeted CAR T cell therapy generates potent and long-lasting CD4-dependent tumor immunity.Sci Transl Med,2014,6(261):261ra151.
[53]Morello A,Sadelain M,Adusumilli PS.Mesothelin-targeted CARS:driving T cells to solid tumors.Cancer Discov,2016,6(2):133-146.
[54]Le DT,Brockstedt DG,Nir-Paz R,et al.A live-attenuated Listeria vaccine(ANZ-100)and a live-attenuated Listeria vaccine expressing mesothelin(CRS-207)for advanced cancers:phase I studies of safety and immune induction.Clin Cancer Res,2012,18(3):858-868.
[55]Le DT,Wang-Gillam A,Picozzi V,et al.Safety and survival with GVAX pancreas prime and Listeria Monocytogenes-expressing mesothelin(CRS-207)boost vaccines for metastatic pancreatic cancer.J Clin Oncol,2015,33(12):1325-1333.
[56]Chang K,Pastan I.Molecular cloning of mesothelin,a differentiation antigen present on mesothelium,mesotheliomas,and ovarian cancers.Proc Natl Acad Sci U S A,1996,93(1):136-140.
[2]Pastan I,Hassan R.Discovery of mosothelin and exploiting it as a target for immunotherapy.J Cancer Res,2014,74(11):2907-2912.
[3]Manzanares Má,Campbell DJW,Maldonado GT,et al.Overexpression of periostin and distinct mesothelin forms predict malignant progression in a rat cholangiocarcinoma model.Hepatol Commun,2018,2(2):155-172.
[4]Burt BM,Lee HS,Lenge De Rosen V,et al.Soluble mesothelin-related peptides to monitor recurrence after resection of pleural mesothelioma.Ann Thorac Surg,2017,104(5):1679-1687.
[5]Asgarov K,Balland J,Tirole C,et al.A new anti-mesothelin antibody targets selectively the membrane-associated form.MAbs,2017,9(3):567-577.
[6]Aguilar-Madrid G,Pesch B,Calderón-Aranda ES,et al.Biomarkers for predicting malignant pleural mesothelioma in a mexican population.Int J Med Sci,2018,15(9):883-891.
[7]Nichetti F,Marra A,Corti F,et al.The role of mesothelin as a diagnostic and therapeutic target in pancreatic ductal adenocarcinoma:a comprehensive review.Target Oncol,2018,13(3):333-351.
[8]Ofek G,McKee K,Yang Y,et al.Relationship between antibody 2F5neutralization of HIV-1 and hydrophobicity of its heavy chain third complementarity-determining region.J Virol,2010,84(6):2955-2962.
[9]Tassev DV,Cheung NK.Monoclonal antibody therapies for solid tumors.Expert Opin Biol Ther,2009,9(3):341-353.
[10]Coelho R,Marcos-Silva L,Ricardo S,et al.Peritoneal dissemination of ovarian cancer:role of MUC16-mesothelin interaction and implications for treatment.Expert Rev Anticancer Ther,2018,18(2):177-186.
[11]Rump A,Morikawa Y,Tanaka M,et al.Binding of ovarian cancer antigen CA125/MLTC16 to mesothelin mediates cell adhesion.J Biol Chem,2004,279(10):9190-9198.
[12]Bharadwaj U,Marin-Muller C,Li M,et al.Mesothelin confers pancreatic cancer cell resistance to TNF-α-induced apoptosis through Akt/PI3K/NF-κB activation and IL-6/Mcl-1 overexpression.Mol Cancer,2011,10:106.
[13]Li M,Bharadwaj U,Zhang R,et al.Mesothelin is a malignant factor and therapeutic vaccine target for pancreatic cancer.Mol Cancer Ther,2008,7(2):286-296.
[14]Bharadwj U,Li M,Chen C,et al.Mesothelin-induced pancreatic cancer cell proliferation involves alteration of cyclin E via activation of signal transducer and activator of transcription protein 3.Mol Cancer Res,2008,6(11):1755-1765.
[15]Cheng WF,Huang CY,Chang MC,et al.High mesothelin correlates with chemoresistance and poor survival in epithelial ovarian carcinoma.J Br Cancer,2009,100(7):1144-1153.
[16]Chang K,Pai LH,Pass H,et al.Monoclonal antibody K1 reacts with epithelial mesothelioma but not lung adenocarcinoma.Am J Surg Pathol,1992,16(3):259-268.
[17]Ordó?ez NG.Application of mesothelin immunostaining in tumor diagnosis.Am J Surg Pathol,2003,27(11):1418-1428.
[18]Argani P,Iacobuzio-Donahue C,Ryu B,et al.Mesothelin is overexpressed in the vast majority of ductal adenocarcinomas of the pancreas:identification of a new pancreatic cancer marker by serial analysis of gene expression(SAGE).Clin Cancer Res,2001,7(12):3862-3868.
[19]Zhu QY,Tu ZX,Li ZS,et al.Expression of mesothelin in pancreatic carcinoma tissue and its clinical significance.Chin J Pancreatology,2005,5(1):17-20.(in Chinese)朱庆云,屠振兴,李兆申,等.Mesothelin在胰腺癌组织的表达及其临床意义.胰腺病学,2005,5(1):17-20.
[20]Chang K,Pastan I.Molecular cloning of mesothelin,a differentiation antigen present on mesothelium,mesotheliomas,and ovarian cancers.Proc Natl Acad Sci U S A,1996,93(1):136-140.
[21]Hanaoka T,Hasegawa K,Kato T,et al.Correlation between tumor mesothelin expression and serum mesothelin in patients with epithelial ovarian carcinoma:a potential noninvasive biomarker for mesothelin-targeted therapy.Mol Diagn Ther,2017,21(2):187-198.
[22]Bayoglu IV,Kucukzeybek BB,Kucukzeybek Y,et al.Prognostic value of mesothelin expression in patients with triple negative and HER2-positive breast cancers.Biomed Pharmacother,2015,70:190-195.
[23]Zhou J,He Y,Zhu Y,et al.Expression and clinical significance of mesothelin in breast cancer.J Clin Oncol,2012,17(11):976-979.(in Chinese)周晶,何烨,朱娅,等.间皮素在乳腺癌中的表达及其临床意义.临床肿瘤学杂志,2012,17(11):976-979.
[24]Miettinen M,Sarlomo-Rikala M.Expression of calretinin,thrombomodulin,keratin 5,and mesothelin in lung carcinomas of different types:an immunohistochemical analysis of 596 tumors in comparison with epithelioid mesotheliomas of the pleura.Am J Surg Pathol,2003,27(2):150-158.
[25]Ho M,Bera TK,Willingham MC,et al.Mesothelin expression in human lung cancer.Clin Cancer Res,2007,13(5):1571-1575.
[26]Baba K,Ishigami S,Arigami T,et al.Mesothelin expression correlates with prolonged patient survival in gastric cancer.J Surg Oncol,2012,105(2):195-199.
[27]Einama T,Homma S,Kamachi H,et al.Luminal membrane expression of mesothelin is a prominent poor prognostic factor for gastric cancer.J Br Cancer,2012,107(1):137-142.
[28]Hassan R,Ebel W,Routh Ier EL,et al.Preclinical evaluation of MORAB-009,a chimeric antibody targeting tumor-associated mesothelin.Cancer Immun,2007,7:20.
[29]Hassan R,Cohen SJ,Phillips M,et al.Phase I clinical trial of the chimeric anti-mesothelin monoclonal antibody MORAb-009 in patients with mesothelin-expressing cancers.Clin Cancer Res,2010,16(24):6132-6138.
[30]Hassan R,Kindler HL,Jahan T,et al.Phase II clinical trial of amatuximab,a chimeric antimesothelin antibody with pemetrexed and cisplatin in advanced unresectable pleural mesothelioma.Clin Cancer Res,2014,20(23):5927-5936.
[31]Nakano T.Systemic treatment of malignant pleural mesothelioma.Gan to Kagaku Ryoho,2017,44(13):2041-2047.
[32]Feng Y,Xiao X,Zhu Z,et al.A novel human monoclonal antibody that binds with high affinity to mesothelin-expressing cells and kills them by antibody-dependent cell-mediated cytotoxicity.Mol Cancer Ther,2009,8(5):1113-1118.
[33]Bendell J,Blumenschein G,Zinner R,et al.Abstract LB-291:First-in-human phase I dose escalation study of a novel anti-mesothelin antibody drug conjugate(ADC),BAY 94-9343,in patients with advanced solid tumors.Cancer Res,2013,73(8 Suppl):291.
[34]Gupta A,Hussein Z,Hassan R,et al.Population pharmacokinetics and exposure-response relationship of amatuximab,an anti-mesothelin monoclonal antibody,in patients with malignant pleural mesothelioma and its application in dose selection.Cancer Chemother Pharmacol,2016,77(4):733-743.
[35]Golfier S,Kopitz C,Kahnert A,et al.Anetumab ratvansine:a novel mesothelin-targeting antibody-drug conjugate cures tumors with heterogeneous target expression favored by bystander effect.Mol Cancer Ther,2014,13(6):1537-1548.
[36]Fujisaka Y,Kurata T,Tanaka K,et al.Phase I study of amatuximab,a novel monoclonal antibody to mesothelin,in Japanese patients with advanced solid tumors.Invest New Drugs,2015,33(2):380-388.
[37]Lindenberg L,Thomas A,Adler S,et al.Safety and biodistribution of111In-amatuximab in patients with mesothelin expressing cancers using Single Photon Emission Computed Tomography-Computed Tomography(SPECT-CT)imaging.Oncotarget,2015,6(6):4496-4504.
[38]Okeley NM,Miyamoto JB,Zhang X,et al.Intracellular activation of SGN 35,a potent anti-CD30 antibody drug conjugate.Clin Cancer Res,2010,16(3):888-897.
[39]Scales SJ,Gupta N,Pacheco G,et al.An antimesothelin-monomethyl auristatine conjugate with potent antitumor activity in ovarian,pancreatic,and mesothelioma models.Mol Cancer Ther,2014,13(11):2630-2640.
[40]Weekes CD,Lamberts LE,Borad MJ,et al.Phase I study of DMOT4039A,an antibody-drug conjugate targeting mesothelin,in patients with unresectable pancreatic or platinum-resistant ovarian cancer.Mol Cancer Ther,2016,15(3):439-447.
[41]Pogue S,Chen X,Alexander S,et al.Fully human antimesothelin antibody drug conjugate demonstrates antitumor effects in human lung cancer models.Clin Cancer Res,2008,14(15 Suppl):A13.
[42]Terrett JA,Pogue SL,Toy K,et al.Human antibodies that bind mesothelin,and uses thereof:US,8399623.2013-03-19.
[43]Nagaya T,Nakamura Y,Sato K,et al.Near infrared photoimmunotherapy with an anti-mesothelin antibody.Oncotarget,2016,7(17):23361-23369.
[44]Bristol-Myers Squibb.A study of BMS-986148 in patients with select advanced solid tumors.2015(2019-04-14)[2019-01-22].https://clinicaltrials.gov/show/NCT02341625.
[45]Kolyvas E,Rudloff M,Poruchynsky M,et al.Mesothelin-targeted immunotoxin RG7787 has synergistic anti-tumor activity when combined with taxanes.Oncotarget,2017,8(6):9189-9199.
[46]Hassan R,Lerner MR,Benbrook D,et al.Antitumor activity of SS(dsFv)PE38 and SS1(dsFv)PE38,recombinant antimesothelin immunotoxins against human gynecologic cancers grown in organotypic culture in vitro.Clin Cancer Res,2002,8(11):3520-3526.
[47]Li Q,Verschraegen CF,Mendoza J,et al.Cytotoxic activity of the recombinant anti-mesothelin immunotoxin,SS1(dsFv)PE38,towards tumor cell lines established from ascites of patients with peritoneal mesotheliomas.Anticancer Res,2004,24(3a):1327-1335.
[48]Hassan R,Bullock S,Premkumar A,et al.Phase I study of SS1P,a recombinant anti-mesothelin immunotoxin given as a bolus I.V.infusion to patients with mesothelin-expressing mesothelioma,ovarian,and pancreatic cancers.Clin Cancer Res,2007,13(17):5144-5149.
[49]Watanabe K,Luo Y,Da T,et al.Pancreatic cancer therapy with combined mesothelin-redirected chimeric antigen receptor T cells and cytokine-armed oncolytic adenoviruses.JCI Insight,2018,3(7):99573.
[50]Lanitis E,Poussin M,Hagemann IS,et al.Redirected antitumor activity of primary human lymphocytes transduced with a fully human anti-mesothelin chimeric receptor.Mol Ther,2012,20(3):633-643.
[51]Beatty GL,Haas AR,Maus MV,et al.Mesothelin-specific chimeric antigen receptor mRNA-engineered T cells induce anti-tumor activity in solid malignancies.Cancer Immunol Res,2014,2(2):112-120.
[52]Adusumilli PS,Cherkassky L,Villena-Vargas J,et al.Regional delivery of mesothelin-targeted CAR T cell therapy generates potent and long-lasting CD4-dependent tumor immunity.Sci Transl Med,2014,6(261):261ra151.
[53]Morello A,Sadelain M,Adusumilli PS.Mesothelin-targeted CARS:driving T cells to solid tumors.Cancer Discov,2016,6(2):133-146.
[54]Le DT,Brockstedt DG,Nir-Paz R,et al.A live-attenuated Listeria vaccine(ANZ-100)and a live-attenuated Listeria vaccine expressing mesothelin(CRS-207)for advanced cancers:phase I studies of safety and immune induction.Clin Cancer Res,2012,18(3):858-868.
[55]Le DT,Wang-Gillam A,Picozzi V,et al.Safety and survival with GVAX pancreas prime and Listeria Monocytogenes-expressing mesothelin(CRS-207)boost vaccines for metastatic pancreatic cancer.J Clin Oncol,2015,33(12):1325-1333.
[56]Chang K,Pastan I.Molecular cloning of mesothelin,a differentiation antigen present on mesothelium,mesotheliomas,and ovarian cancers.Proc Natl Acad Sci U S A,1996,93(1):136-140.