Mesothelin: An Immunotherapeutic Target beyond Solid Tumors
Abstract
:Simple Summary
Abstract
1. Introduction
2. Structure and Function of Mesothelin
3. Mesothelin Binding Partners
4. Role of Mesothelin in Cancers and Signaling
5. Regulation of Mesothelin Expression
6. Mesothelin Targeting Therapies
6.1. Immunotoxins and Monoclonal Antibodies
6.2. Vaccines
6.3. Antibody–Drug Conjugates
6.4. Chimeric Antigen Receptor T Cells and T Cell Receptor Fusion Constructs
CAR-T Cell Alterations
6.5. Chimeric Antigen Receptor Natural Killer Cells
6.6. Bispecific T Cell-Engaging Molecules
6.7. Targeted Alpha Therapies
6.8. Impact of Mesothelin Shedding on Mesothelin-Targeting Therapies
7. Role of Mesothelin in Hematological Malignancies
8. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Phase | Tumor Type | Mechanism | NCT Number | Reference |
---|---|---|---|---|
Pre-clinical | MSLN+ AML | anti-MSLN CAR-T cells | N/A | [61] |
Pre-clinical | MSLN+ AML | anti-MSLN NK cells | N/A | [62] |
Pre-clinical | MSLN+ AML | BiTEs | N/A | [63] |
Pre-clinical | MSLN+ AML | Anetumab ravtansine | N/A | [11] |
Early Phase 1 | Ovarian cancer | anti-MSLN CAR-T cells, fludarabine and cyclophosphamide | NCT03814447 | |
Phase 1 | Refractory malignant solid neoplasm | TCR-T cells, cyclophosphamide and fludarabine | NCT04809766 | |
Phase 1 | Solid tumors | anti-MSLN CAR-T cells | NCT03545815 | [64] |
Phase 1 | Lung adenocarcinoma, ovarian cancer, peritoneal carcinoma | anti-MSLN CAR-T cells | NCT03054298 | [65] |
Phase 1 | Malignant pleural mesothelioma | anti-MSLN CAR-T cells and cyclophosphamide | NCT04577326 | |
Phase 1 | MSLN+ neoplasms, epithelioid mesothelioma, cholangiocarcinoma, pancreatic adenocarcinoma | LMB-100 and Tofacitinib | NCT04034238 | [66] |
Phase 1 | Mesothelioma | LMB-100 and Ipilimumab | NCT04840615 | |
Phase 1 | Advanced recurrent epithelioid mesothelioma, serous ovarian cancer, metastatic or locally advanced pancreatic ductal adenocarcinoma | BAY2287411 (MSLN-TTC) | NCT03507452 | [67] |
Phase 1, 2 | Advanced MSLN+ tumors | HPN536 | NCT03872206 | |
Phase 1, 2 | Pancreatic adenocarcinoma | Anetumab ravtansine, gemcitabine hydrochloride, Ipilimumab and Nivolumab | NCT03816358 | |
Phase 2 | Fallopian tube endometrioid adenocarcinoma, high grade fallopian tube and ovarian serous adenocarcinoma | Anetumab ravtansine, Bevacizumab and paclitaxel | NCT03587311 | |
Phase 2 | Non-small cell lung cancer | LMB-100 and Pembrolizumab | NCT04027946 | |
Completed | Malignant. Mesothelioma | SS1P, pentostatin, and cyclophosphamide | NCT01362790 | |
Completed | Pancreatic cancer | GVAX and CRS-207 | NCT02243371 | [68] |
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Faust, J.R.; Hamill, D.; Kolb, E.A.; Gopalakrishnapillai, A.; Barwe, S.P. Mesothelin: An Immunotherapeutic Target beyond Solid Tumors. Cancers 2022, 14, 1550. https://doi.org/10.3390/cancers14061550
Faust JR, Hamill D, Kolb EA, Gopalakrishnapillai A, Barwe SP. Mesothelin: An Immunotherapeutic Target beyond Solid Tumors. Cancers. 2022; 14(6):1550. https://doi.org/10.3390/cancers14061550
Chicago/Turabian StyleFaust, Joshua R., Darcy Hamill, Edward Anders Kolb, Anilkumar Gopalakrishnapillai, and Sonali P. Barwe. 2022. "Mesothelin: An Immunotherapeutic Target beyond Solid Tumors" Cancers 14, no. 6: 1550. https://doi.org/10.3390/cancers14061550