Using the Power of Junctional Adhesion Molecules Combined with the Target of CAR-T to Inhibit Cancer Proliferation, Metastasis and Eradicate Tumors
Decades of evidence suggest that alterations in the adhesion properties of neoplastic cells endow them with an invasive and migratory phenotype. Tight junctions (TJs) are present in endothelial and epithelial cells. Tumors arise from such tissues, thus, the role of TJ proteins in the tumor microenvi...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-02-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/10/2/381 |
| _version_ | 1797482412185223168 |
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| author | Christopher Mendoza Dario Mizrachi |
| author_facet | Christopher Mendoza Dario Mizrachi |
| author_sort | Christopher Mendoza |
| collection | DOAJ |
| description | Decades of evidence suggest that alterations in the adhesion properties of neoplastic cells endow them with an invasive and migratory phenotype. Tight junctions (TJs) are present in endothelial and epithelial cells. Tumors arise from such tissues, thus, the role of TJ proteins in the tumor microenvironment is highly relevant. In the TJ, junctional adhesion molecules (JAM) play a key role in assembly of the TJ and control of cell–cell adhesion. Reprogramming of immune cells using chimeric antigen receptors (CAR) to allow for target recognition and eradication of tumors is an FDA approved therapy. The best-studied CAR-T cells recognize CD19, a B-cell surface molecule. CD19 is not a unique marker for tumors, liquid or solid. To address this limitation, we developed a biologic containing three domains: (1) pH-low-insertion peptide (pHLIP), which recognizes the low pH of the cancer cells, leading to the insertion of the peptide into the plasma membrane. (2) An extracellular domain of JAM proteins that fosters cell–cell interactions. (3) CD19 to be targeted by CAR-T cells. Our modular design only targets cancer cells and when coupled with anti-CD19 CAR-T cells, it decreases proliferation and metastasis in at least two cancer cell lines. |
| first_indexed | 2024-03-09T22:31:59Z |
| format | Article |
| id | doaj.art-79dab5a5a90e48ff8c49b1d219142e3b |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-09T22:31:59Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-79dab5a5a90e48ff8c49b1d219142e3b2023-11-23T18:54:42ZengMDPI AGBiomedicines2227-90592022-02-0110238110.3390/biomedicines10020381Using the Power of Junctional Adhesion Molecules Combined with the Target of CAR-T to Inhibit Cancer Proliferation, Metastasis and Eradicate TumorsChristopher Mendoza0Dario Mizrachi1Department of Cell Biology and Physiology, College of Life Sciences, Brigham Young University, Provo, UT 84602, USADepartment of Cell Biology and Physiology, College of Life Sciences, Brigham Young University, Provo, UT 84602, USADecades of evidence suggest that alterations in the adhesion properties of neoplastic cells endow them with an invasive and migratory phenotype. Tight junctions (TJs) are present in endothelial and epithelial cells. Tumors arise from such tissues, thus, the role of TJ proteins in the tumor microenvironment is highly relevant. In the TJ, junctional adhesion molecules (JAM) play a key role in assembly of the TJ and control of cell–cell adhesion. Reprogramming of immune cells using chimeric antigen receptors (CAR) to allow for target recognition and eradication of tumors is an FDA approved therapy. The best-studied CAR-T cells recognize CD19, a B-cell surface molecule. CD19 is not a unique marker for tumors, liquid or solid. To address this limitation, we developed a biologic containing three domains: (1) pH-low-insertion peptide (pHLIP), which recognizes the low pH of the cancer cells, leading to the insertion of the peptide into the plasma membrane. (2) An extracellular domain of JAM proteins that fosters cell–cell interactions. (3) CD19 to be targeted by CAR-T cells. Our modular design only targets cancer cells and when coupled with anti-CD19 CAR-T cells, it decreases proliferation and metastasis in at least two cancer cell lines.https://www.mdpi.com/2227-9059/10/2/381junctional adhesion moleculechimeric antigen receptorsize-exclusion chromatography |
| spellingShingle | Christopher Mendoza Dario Mizrachi Using the Power of Junctional Adhesion Molecules Combined with the Target of CAR-T to Inhibit Cancer Proliferation, Metastasis and Eradicate Tumors Biomedicines junctional adhesion molecule chimeric antigen receptor size-exclusion chromatography |
| title | Using the Power of Junctional Adhesion Molecules Combined with the Target of CAR-T to Inhibit Cancer Proliferation, Metastasis and Eradicate Tumors |
| title_full | Using the Power of Junctional Adhesion Molecules Combined with the Target of CAR-T to Inhibit Cancer Proliferation, Metastasis and Eradicate Tumors |
| title_fullStr | Using the Power of Junctional Adhesion Molecules Combined with the Target of CAR-T to Inhibit Cancer Proliferation, Metastasis and Eradicate Tumors |
| title_full_unstemmed | Using the Power of Junctional Adhesion Molecules Combined with the Target of CAR-T to Inhibit Cancer Proliferation, Metastasis and Eradicate Tumors |
| title_short | Using the Power of Junctional Adhesion Molecules Combined with the Target of CAR-T to Inhibit Cancer Proliferation, Metastasis and Eradicate Tumors |
| title_sort | using the power of junctional adhesion molecules combined with the target of car t to inhibit cancer proliferation metastasis and eradicate tumors |
| topic | junctional adhesion molecule chimeric antigen receptor size-exclusion chromatography |
| url | https://www.mdpi.com/2227-9059/10/2/381 |
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