Radioimmunotherapy for Malignant Mesothelioma Targeting C-ERC/Mesothelin

  • Pharmaceuticals (Basel). 2026 Mar 18;19(3):501. doi: 10.3390/ph19030501.
Hirofumi Hanaoka  1  2 ,  Aiko Yamaguchi  1  3 ,  Masahiro Maeda  4 ,  Tatsuya Segawa  4 ,  Noboru Oriuchi  5  6
Affiliations
  • 1. Graduate School of Medicine, Gunma University, 3-39-22 Showa-machi, Maebashi 371-8511, Japan.
  • 2. Near InfraRed Photo-ImmunoTherapy Research Institute, Kansai Medical University, 2-5-1 Shin-machi, Hirakata 573-1010, Japan.
  • 3. Radiopharmaceuticals for Advanced Diagnostic Imaging and Therapy R&D Platform, Therapeutics Discovery Division, The University of Texas MD Anderson Cancer Center, 1881 East Rd., Houston, TX 77054, USA.
  • 4. Immuno-Biological Laboratories Co, Ltd., 1091-1 Naka Aza-Higashida, Fujioka 375-0005, Japan.
  • 5. Advanced Clinical Research Center, Fukushima Global Medical Science Center, Fukushima Medical University, Fukushima 960-1295, Japan.
  • 6. Jyoban Hospital of Tokiwa Foundation, Kaminodai 57, Jyoban Kamiyunagaya, Iwaki 972-8322, Japan.
PMID: 41901346 DOI: 10.3390/ph19030501
Abstract

Background/Objectives: Malignant mesothelioma has a poor prognosis and limited therapeutic options. C-ERC/Mesothelin is highly expressed in mesotheliomas and is a potential target for radioimmunotherapy (RIT). This study evaluated the radiolabeled anti-C-ERC/Mesothelin antibody mAb 22A31 as a therapeutic agent. Methods: C-ERC/Mesothelin expression in mesothelioma cell lines was assessed by Western blotting, and the specific binding of 125I-labeled mAb 22A31 was examined. Biodistribution of 111In-labeled mAb 22A31 was evaluated in a mesothelioma cell line, MSTO-211H tumor-bearing mice. The therapeutic efficacy of 90Y-labeled mAb 22A31 was evaluated in subcutaneous and pleural dissemination models. Results: mAb 22A31 showed specific binding considering the level of C-ERC/Mesothelin expression in each mesothelioma cell line. 111In-mAb 22A31 accumulated in Tumors with minimal uptake in normal tissues. 90Y-mAb 22A31 significantly delayed the growth of subcutaneous Tumors and improved survival in a pleural dissemination model. Conclusions: Radiolabeled mAb 22A31 specifically targeted C-ERC/Mesothelin and demonstrated therapeutic efficacy in a mesothelioma xerograph model. Therefore, 90Y-mAb 22A31 is a promising RIT agent and supports the further development of C-ERC/mesothelin-targeted therapy for mesothelioma.

Keywords
C-ERC/mesothelin; malignant mesothelioma; radioimmunotherapy.