» Articles » PMID: 27863199

Mesothelin Immunotherapy for Cancer: Ready for Prime Time?

Overview
Journal J Clin Oncol
Specialty Oncology
Date 2016 Nov 19
PMID 27863199
Citations 186
Authors
Affiliations
Soon will be listed here.
Abstract

Mesothelin is a tumor antigen that is highly expressed in many human cancers, including malignant mesothelioma and pancreatic, ovarian, and lung adenocarcinomas. It is an attractive target for cancer immunotherapy because its normal expression is limited to mesothelial cells, which are dispensable. Several antibody-based therapeutic agents as well as vaccine and T-cell therapies directed at mesothelin are undergoing clinical evaluation. These include antimesothelin immunotoxins (SS1P, RG7787/LMB-100), chimeric antimesothelin antibody (amatuximab), mesothelin-directed antibody drug conjugates (anetumab ravtansine, DMOT4039A, BMS-986148), live attenuated Listeria monocytogenes-expressing mesothelin (CRS-207, JNJ-64041757), and chimeric antigen receptor T-cell therapies. Two antimesothelin agents are currently in multicenter clinical registration trials for malignant mesothelioma: amatuximab in the first-line setting and anetumab ravtansine as second-line therapy. Phase II randomized clinical trials of CRS-207 as a boosting agent and in combination with immune checkpoint inhibition for pancreatic cancer are nearing completion. These ongoing studies will define the utility of mesothelin immunotherapy for treating cancer.

Citing Articles

Mesothelin (MSLN) is Highly Expressed in Triple Negative Breast Cancer and is Associated with Enhanced Cell Proliferation and Proinflammatory Tumor Microenvironment.

Hagerty B, Sato T, Wu R, Ishikawa T, Takabe K Ann Surg Oncol. 2025; .

PMID: 40080368 DOI: 10.1245/s10434-025-17117-y.


Advancing Immunotherapy in Pancreatic Cancer: A Brief Review of Emerging Adoptive Cell Therapies.

Sherpally D, Manne A Cancers (Basel). 2025; 17(4).

PMID: 40002184 PMC: 11853216. DOI: 10.3390/cancers17040589.


Microbiome dysbiosis, neutrophil recruitment and mesenchymal transition of mesothelial cells promotes peritoneal metastasis of colorectal cancer.

Li Q, Xiao Y, Han L, Luo W, Dai W, Fang H Nat Cancer. 2025; .

PMID: 39966610 DOI: 10.1038/s43018-025-00910-9.


Excess shed mesothelin disrupts pancreatic cancer cell clustering to impair peritoneal colonization.

Ewa T, Panchwagh N, Tai C, Avula L, Joseph S, Rudloff M FASEB J. 2024; 38(24):e70247.

PMID: 39673668 PMC: 11646052. DOI: 10.1096/fj.202400446R.


Persistence of activated anti-mesothelin hYP218 chimeric antigen receptor T cells in the tumour is associated with efficacy in gastric and colorectal carcinomas.

Mir S, Venugopalan A, Zhang J, Nair N, Sengupta M, Khanal M Clin Transl Med. 2024; 14(11):e70057.

PMID: 39548594 PMC: 11567854. DOI: 10.1002/ctm2.70057.


References
1.
Le D, Wang-Gillam A, Picozzi V, Greten T, Crocenzi T, Springett G . 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):1325-33. PMC: 4397277. DOI: 10.1200/JCO.2014.57.4244. View

2.
Tozbikian G, Brogi E, Kadota K, Catalano J, Akram M, Patil S . Mesothelin expression in triple negative breast carcinomas correlates significantly with basal-like phenotype, distant metastases and decreased survival. PLoS One. 2014; 9(12):e114900. PMC: 4266616. DOI: 10.1371/journal.pone.0114900. View

3.
Hassan R, Kreitman R, Pastan I, Willingham M . Localization of mesothelin in epithelial ovarian cancer. Appl Immunohistochem Mol Morphol. 2005; 13(3):243-7. DOI: 10.1097/01.pai.00000141545.36485.d6. View

4.
Brockstedt D, Giedlin M, Leong M, Bahjat K, Gao Y, Luckett W . Listeria-based cancer vaccines that segregate immunogenicity from toxicity. Proc Natl Acad Sci U S A. 2004; 101(38):13832-7. PMC: 518841. DOI: 10.1073/pnas.0406035101. View

5.
Zhang Y, Chertov O, Zhang J, Hassan R, Pastan I . Cytotoxic activity of immunotoxin SS1P is modulated by TACE-dependent mesothelin shedding. Cancer Res. 2011; 71(17):5915-22. PMC: 3165076. DOI: 10.1158/0008-5472.CAN-11-0466. View