Skip to main content
Top
Published in: Journal of Hematology & Oncology 1/2017

Open Access 01-12-2017 | Review

Anti-claudin 18.2 antibody as new targeted therapy for advanced gastric cancer

Authors: Prabhsimranjot Singh, Sudhamshi Toom, Yiwu Huang

Published in: Journal of Hematology & Oncology | Issue 1/2017

Login to get access

Abstract

Targeted therapy and immunotherapy have revolutionized treatment of various cancers in the past decade. Despite targeted therapy with trastuzumab in Her2-positive gastric cancer patients, survival has been dismal, mostly due to disease progression and toxicity related to the treatments. One area of active development is looking for ideal monoclonal antibodies (IMAB) specific to the proteins only on the tumor and hence avoiding unnecessary side effects. Claudin proteins with isoform 2 are one such protein, specific for several cancers, particularly gastric cancer and its metastases, leading to the development of anti-claudin 18.2 specific antibody, claudiximab. This review will highlight the latest development of claudiximab as first in class IMAB for the treatment of gastric cancer.
Literature
1.
go back to reference Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87–108.CrossRefPubMed Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87–108.CrossRefPubMed
2.
go back to reference Buzzoni R, Bajetta E, Di Bartolomeo M, Miceli R, Beretta E, Ferrario E, Mariani L. Pathological features as predictors of recurrence after radical resection of gastric cancer. Br J Surg. 2006;93(2):205–9.CrossRefPubMed Buzzoni R, Bajetta E, Di Bartolomeo M, Miceli R, Beretta E, Ferrario E, Mariani L. Pathological features as predictors of recurrence after radical resection of gastric cancer. Br J Surg. 2006;93(2):205–9.CrossRefPubMed
3.
go back to reference Macdonald JS, Smalley SR, Benedetti J, Hundahl SA, Estes NC, Stemmermann GN, Haller DG, Ajani JA, Gunderson LL, Jessup JM, et al. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med. 2001;345(10):725–30.CrossRefPubMed Macdonald JS, Smalley SR, Benedetti J, Hundahl SA, Estes NC, Stemmermann GN, Haller DG, Ajani JA, Gunderson LL, Jessup JM, et al. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med. 2001;345(10):725–30.CrossRefPubMed
4.
go back to reference Wagner AD, Unverzagt S, Grothe W, Kleber G, Grothey A, Haerting J, Fleig WE. Chemotherapy for advanced gastric cancer. Cochrane Database Syst Rev. 2010;3:CD004064. Wagner AD, Unverzagt S, Grothe W, Kleber G, Grothey A, Haerting J, Fleig WE. Chemotherapy for advanced gastric cancer. Cochrane Database Syst Rev. 2010;3:CD004064.
5.
go back to reference Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010;376(9742):687–97.CrossRefPubMed Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010;376(9742):687–97.CrossRefPubMed
6.
go back to reference Wilke H, Muro K, Van Cutsem E, Oh SC, Bodoky G, Shimada Y, Hironaka S, Sugimoto N, Lipatov O, Kim TY, et al. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol. 2014;15(11):1224–35.CrossRefPubMed Wilke H, Muro K, Van Cutsem E, Oh SC, Bodoky G, Shimada Y, Hironaka S, Sugimoto N, Lipatov O, Kim TY, et al. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol. 2014;15(11):1224–35.CrossRefPubMed
7.
go back to reference Ansell SM, Lesokhin AM, Borrello I, Halwani A, Scott EC, Gutierrez M, Schuster SJ, Millenson MM, Cattry D, Freeman GJ, et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin’s lymphoma. N Engl J Med. 2015;372(4):311–9.CrossRefPubMed Ansell SM, Lesokhin AM, Borrello I, Halwani A, Scott EC, Gutierrez M, Schuster SJ, Millenson MM, Cattry D, Freeman GJ, et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin’s lymphoma. N Engl J Med. 2015;372(4):311–9.CrossRefPubMed
8.
go back to reference Brahmer J, Reckamp KL, Baas P, Crino L, Eberhardt WE, Poddubskaya E, Antonia S, Pluzanski A, Vokes EE, Holgado E, et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med. 2015;373(2):123–35.CrossRefPubMedPubMedCentral Brahmer J, Reckamp KL, Baas P, Crino L, Eberhardt WE, Poddubskaya E, Antonia S, Pluzanski A, Vokes EE, Holgado E, et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med. 2015;373(2):123–35.CrossRefPubMedPubMedCentral
9.
go back to reference Garon EB, Rizvi NA, Hui R, Leighl N, Balmanoukian AS, Eder JP, Patnaik A, Aggarwal C, Gubens M, Horn L, et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med. 2015;372(21):2018–28.CrossRefPubMed Garon EB, Rizvi NA, Hui R, Leighl N, Balmanoukian AS, Eder JP, Patnaik A, Aggarwal C, Gubens M, Horn L, et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med. 2015;372(21):2018–28.CrossRefPubMed
10.
go back to reference Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, Schadendorf D, Dummer R, Smylie M, Rutkowski P, et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med. 2015;373(1):23–34.CrossRefPubMed Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, Schadendorf D, Dummer R, Smylie M, Rutkowski P, et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med. 2015;373(1):23–34.CrossRefPubMed
11.
go back to reference Postow MA, Chesney J, Pavlick AC, Robert C, Grossmann K, McDermott D, Linette GP, Meyer N, Giguere JK, Agarwala SS, et al. Nivolumab and ipilimumab versus ipilimumab in untreated melanoma. N Engl J Med. 2015;372(21):2006–17.CrossRefPubMed Postow MA, Chesney J, Pavlick AC, Robert C, Grossmann K, McDermott D, Linette GP, Meyer N, Giguere JK, Agarwala SS, et al. Nivolumab and ipilimumab versus ipilimumab in untreated melanoma. N Engl J Med. 2015;372(21):2006–17.CrossRefPubMed
12.
go back to reference Furqan M, Mukhi N, Lee B, Liu D. Dysregulation of JAK-STAT pathway in hematological malignancies and JAK inhibitors for clinical application. Biomark Res. 2013;1(1):5.CrossRefPubMedPubMedCentral Furqan M, Mukhi N, Lee B, Liu D. Dysregulation of JAK-STAT pathway in hematological malignancies and JAK inhibitors for clinical application. Biomark Res. 2013;1(1):5.CrossRefPubMedPubMedCentral
13.
go back to reference Yu J, Zhang Y, Leung LH, Liu L, Yang F, Yao X. Efficacy and safety of angiogenesis inhibitors in advanced gastric cancer: a systematic review and meta-analysis. J Hematol Oncol. 2016;9(1):111.CrossRefPubMedPubMedCentral Yu J, Zhang Y, Leung LH, Liu L, Yang F, Yao X. Efficacy and safety of angiogenesis inhibitors in advanced gastric cancer: a systematic review and meta-analysis. J Hematol Oncol. 2016;9(1):111.CrossRefPubMedPubMedCentral
14.
go back to reference Wang X, Wang C, Zhang X, Hua R, Gan L, Huang M, Zhao L, Ni S, Guo W. Bmi-1 regulates stem cell-like properties of gastric cancer cells via modulating miRNAs. J Hematol Oncol. 2016;9(1):90.CrossRefPubMedPubMedCentral Wang X, Wang C, Zhang X, Hua R, Gan L, Huang M, Zhao L, Ni S, Guo W. Bmi-1 regulates stem cell-like properties of gastric cancer cells via modulating miRNAs. J Hematol Oncol. 2016;9(1):90.CrossRefPubMedPubMedCentral
15.
go back to reference Liu J, Pan C, Guo L, Wu M, Guo J, Peng S, Wu Q, Zuo Q. A new mechanism of trastuzumab resistance in gastric cancer: MACC1 promotes the Warburg effect via activation of the PI3K/AKT signaling pathway. J Hematol Oncol. 2016;9(1):76.CrossRefPubMedPubMedCentral Liu J, Pan C, Guo L, Wu M, Guo J, Peng S, Wu Q, Zuo Q. A new mechanism of trastuzumab resistance in gastric cancer: MACC1 promotes the Warburg effect via activation of the PI3K/AKT signaling pathway. J Hematol Oncol. 2016;9(1):76.CrossRefPubMedPubMedCentral
16.
17.
go back to reference Furuse M, Fujita K, Hiiragi T, Fujimoto K, Tsukita S. Claudin-1 and -2: novel integral membrane proteins localizing at tight junctions with no sequence similarity to occludin. J Cell Biol. 1998;141(7):1539–50.CrossRefPubMedPubMedCentral Furuse M, Fujita K, Hiiragi T, Fujimoto K, Tsukita S. Claudin-1 and -2: novel integral membrane proteins localizing at tight junctions with no sequence similarity to occludin. J Cell Biol. 1998;141(7):1539–50.CrossRefPubMedPubMedCentral
18.
go back to reference Swisshelm K, Macek R, Kubbies M. Role of claudins in tumorigenesis. Adv Drug Deliv Rev. 2005;57(6):919–28.CrossRefPubMed Swisshelm K, Macek R, Kubbies M. Role of claudins in tumorigenesis. Adv Drug Deliv Rev. 2005;57(6):919–28.CrossRefPubMed
19.
go back to reference Morin PJ. Claudin proteins in human cancer: promising new targets for diagnosis and therapy. Cancer Res. 2005;65(21):9603–6.CrossRefPubMed Morin PJ. Claudin proteins in human cancer: promising new targets for diagnosis and therapy. Cancer Res. 2005;65(21):9603–6.CrossRefPubMed
20.
go back to reference Resnick MB, Konkin T, Routhier J, Sabo E, Pricolo VE. Claudin-1 is a strong prognostic indicator in stage II colonic cancer: a tissue microarray study. Mod Pathol. 2005;18(4):511–8.CrossRefPubMed Resnick MB, Konkin T, Routhier J, Sabo E, Pricolo VE. Claudin-1 is a strong prognostic indicator in stage II colonic cancer: a tissue microarray study. Mod Pathol. 2005;18(4):511–8.CrossRefPubMed
21.
go back to reference Sanada Y, Oue N, Mitani Y, Yoshida K, Nakayama H, Yasui W. Down-regulation of the claudin-18 gene, identified through serial analysis of gene expression data analysis, in gastric cancer with an intestinal phenotype. J Pathol. 2006;208(5):633–42.CrossRefPubMed Sanada Y, Oue N, Mitani Y, Yoshida K, Nakayama H, Yasui W. Down-regulation of the claudin-18 gene, identified through serial analysis of gene expression data analysis, in gastric cancer with an intestinal phenotype. J Pathol. 2006;208(5):633–42.CrossRefPubMed
22.
go back to reference Cheung ST, Leung KL, Ip YC, Chen X, Fong DY, Ng IO, Fan ST, So S. Claudin-10 expression level is associated with recurrence of primary hepatocellular carcinoma. Clin Cancer Res. 2005;11(2 Pt 1):551–6.PubMed Cheung ST, Leung KL, Ip YC, Chen X, Fong DY, Ng IO, Fan ST, So S. Claudin-10 expression level is associated with recurrence of primary hepatocellular carcinoma. Clin Cancer Res. 2005;11(2 Pt 1):551–6.PubMed
23.
go back to reference Sahin U, Koslowski M, Dhaene K, Usener D, Brandenburg G, Seitz G, Huber C, Tureci O. Claudin-18 splice variant 2 is a pan-cancer target suitable for therapeutic antibody development. Clin Cancer Res. 2008;14(23):7624–34.CrossRefPubMed Sahin U, Koslowski M, Dhaene K, Usener D, Brandenburg G, Seitz G, Huber C, Tureci O. Claudin-18 splice variant 2 is a pan-cancer target suitable for therapeutic antibody development. Clin Cancer Res. 2008;14(23):7624–34.CrossRefPubMed
24.
go back to reference Schuler MH, Zvirbule Z, Lordick F, Krilova A, Helbig U, Schulze-Bergkamen H, Thuss-Patience P-C, Wichert G-V, Schulmann K, Trarbach T, Bauer S, Mueller C, Al-Batran S-E, Huber C, Sahin U, Tureci O. Safety, tolerability, and efficacy of the first-in-class antibody IMAB362 targeting claudin 18.2 in patients with metastatic gastroesophageal adenocarcinomas. ASCO Meet Abstr. 2013;31:4080. Schuler MH, Zvirbule Z, Lordick F, Krilova A, Helbig U, Schulze-Bergkamen H, Thuss-Patience P-C, Wichert G-V, Schulmann K, Trarbach T, Bauer S, Mueller C, Al-Batran S-E, Huber C, Sahin U, Tureci O. Safety, tolerability, and efficacy of the first-in-class antibody IMAB362 targeting claudin 18.2 in patients with metastatic gastroesophageal adenocarcinomas. ASCO Meet Abstr. 2013;31:4080.
25.
go back to reference Sahin U, Al-Batran S-E, Hozaeel W, Zvirbule Z, Freiberg-Richter J, Lordick F, Just M, Bitzer M, Thuss-Patience P-C, Krilova A, Brass V, Mueller C, Daalman E, Tureci O. IMAB362 plus zoledronic acid (ZA) and interleukin-2 (IL-2) in patients (pts) with advanced gastroesophageal cancer (GEC): clinical activity and safety data from the PILOT phase I trial. ASCO Meet Abstr. 2015;33:e15079. Sahin U, Al-Batran S-E, Hozaeel W, Zvirbule Z, Freiberg-Richter J, Lordick F, Just M, Bitzer M, Thuss-Patience P-C, Krilova A, Brass V, Mueller C, Daalman E, Tureci O. IMAB362 plus zoledronic acid (ZA) and interleukin-2 (IL-2) in patients (pts) with advanced gastroesophageal cancer (GEC): clinical activity and safety data from the PILOT phase I trial. ASCO Meet Abstr. 2015;33:e15079.
26.
go back to reference Trarbach T, Schuler M, Zvirbule Z, Lordick F, Krilova A, Helbig U, Schulze-Bergkamen H, Thuss-Patience P-C, Wichert G, Schmiegel W, Bauer S, Müller C, Al-Batran S, Huber C, Maurus D, Kühnle M, Sahin U, Türeci O. 636P. Efficacy and safety of multiple doses of IMAB362 in patients with advanced gastroesophageal cancer: results of a phase II study. Ann Oncol. 2014;25(4 Supplement):iv218.CrossRef Trarbach T, Schuler M, Zvirbule Z, Lordick F, Krilova A, Helbig U, Schulze-Bergkamen H, Thuss-Patience P-C, Wichert G, Schmiegel W, Bauer S, Müller C, Al-Batran S, Huber C, Maurus D, Kühnle M, Sahin U, Türeci O. 636P. Efficacy and safety of multiple doses of IMAB362 in patients with advanced gastroesophageal cancer: results of a phase II study. Ann Oncol. 2014;25(4 Supplement):iv218.CrossRef
27.
go back to reference Al-Batran S-E, Schuler M, Zvirbule Z, Manikhas G, Lordick F, Tureci O, Huber C, Sahin U. LBA-06. IMAB362: a novel immunotherapeutic antibody targeting the tight-junction protein component CLAUDIN18.2 in gastric cancer. Ann Oncol. 2016;27(2 Supplement):ii141–2.CrossRef Al-Batran S-E, Schuler M, Zvirbule Z, Manikhas G, Lordick F, Tureci O, Huber C, Sahin U. LBA-06. IMAB362: a novel immunotherapeutic antibody targeting the tight-junction protein component CLAUDIN18.2 in gastric cancer. Ann Oncol. 2016;27(2 Supplement):ii141–2.CrossRef
28.
go back to reference Al-Batran S, Schuler M, Zvirbule Z, Manikhas G, Lordick F, Rusyn A, Vynnyk Y, Vynnychenko I, Fadeeva N, Nechaeva M, Dudov A, Gotovkin E, Pecheniy A, Bazin I, Bondarenko I, Melichar B, Mueller C, Huber C, Tureci O, Sahin U. FAST: an international, multicenter, randomized, phase II trial of epirubicin, oxaliplatin, and capecitabine (EOX) with or without IMAB362, a first-in-class anti-CLDN18.2 antibody, as first-line therapy in patients with advanced CLDN18.2+ gastric and gastroesophageal junction (GEJ) adenocarcinoma. ASCO Meet Abstr. 2016;34:LBA4001. Al-Batran S, Schuler M, Zvirbule Z, Manikhas G, Lordick F, Rusyn A, Vynnyk Y, Vynnychenko I, Fadeeva N, Nechaeva M, Dudov A, Gotovkin E, Pecheniy A, Bazin I, Bondarenko I, Melichar B, Mueller C, Huber C, Tureci O, Sahin U. FAST: an international, multicenter, randomized, phase II trial of epirubicin, oxaliplatin, and capecitabine (EOX) with or without IMAB362, a first-in-class anti-CLDN18.2 antibody, as first-line therapy in patients with advanced CLDN18.2+ gastric and gastroesophageal junction (GEJ) adenocarcinoma. ASCO Meet Abstr. 2016;34:LBA4001.
29.
go back to reference Cunningham D, Starling N, Rao S, Iveson T, Nicolson M, Coxon F, Middleton G, Daniel F, Oates J, Norman AR, et al. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med. 2008;358(1):36–46.CrossRefPubMed Cunningham D, Starling N, Rao S, Iveson T, Nicolson M, Coxon F, Middleton G, Daniel F, Oates J, Norman AR, et al. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med. 2008;358(1):36–46.CrossRefPubMed
Metadata
Title
Anti-claudin 18.2 antibody as new targeted therapy for advanced gastric cancer
Authors
Prabhsimranjot Singh
Sudhamshi Toom
Yiwu Huang
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Journal of Hematology & Oncology / Issue 1/2017
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/s13045-017-0473-4

Other articles of this Issue 1/2017

Journal of Hematology & Oncology 1/2017 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine