4.7 Review

Mesothelin as a biomarker for targeted therapy

Journal

BIOMARKER RESEARCH
Volume 7, Issue 1, Pages -

Publisher

BMC
DOI: 10.1186/s40364-019-0169-8

Keywords

Mesothelin; Biomarker; Targeted therapy; Immunotherapy; CAR-T

Funding

  1. Guangzhou science and technology plan project [201907010042, 201904010473]
  2. National Major Scientific and Technological Special Project for Significant New Drugs Development [SQ2018ZX090201]
  3. Strategic Priority Research Program of the Chinese Academy of Sciences [XDB19030205, XDA12050305]
  4. Guangdong Provincial Applied Science and Technology Research & Development Program [2016B020237006]
  5. Guangdong Special Support Program [2017TX04R102]
  6. Frontier and key technology innovation special grant from the Department of Science and Technology of Guangdong province [2015B020227003]
  7. Natural Science Fund of Guangdong Province [2014A030306028, 2017A030310381]
  8. National Natural Science Foundation of China (NSFC) [81773301, 81700156, 81870121, 81873847]
  9. Frontier Research Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory [2018GZR110105003]
  10. Science and Technology Planning Project of Guangdong Province, China [2017B030314056]
  11. Guangzhou Medical University High-level University Construction Research Startup Fund [B195002004013]
  12. Research Program of Hefei Institute of Stem Cell and Regenerative Medicine [2019YF001]

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CAR-T cell therapy targeting CD19 has achieved remarkable success in the treatment of B cell malignancies, while various solid malignancies are still refractory for lack of suitable target. In recent years, a large number of studies have sought to find suitable targets with low on target, off tumor concern for the treatment of solid tumors. Mesothelin (MSLN), a tumor-associated antigen broadly overexpressed on various malignant tumor cells, while its expression is generally limited to normal mesothelial cells, is an attractive candidate for targeted therapy. Strategies targeting MSLN, including antibody-based drugs, vaccines and CAR-T therapies, have been assessed in a large number of preclinical investigations and clinical trials. In particular, the development of CAR-T therapy has shown great promise as a treatment for various types of cancers. The safety, efficacy, doses, and pharmacokinetics of relevant strategies have been evaluated in many clinical trials. This review is intended to provide a brief overview of the characteristics of mesothelin and the development of strategies targeting MSLN for solid tumors. Further, we discussed the challenges and proposed potential strategies to improve the efficacy of MSLN targeted immunotherapy.

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