The PTPN2/PTPN1 inhibitor ABBV-CLS-484 unleashes potent anti-tumour immunity

• Published in: Nature (London) Vol. 622; no. 7984; pp. 850 - 862
• Main Authors: Baumgartner, Christina K., Ebrahimi-Nik, Hakimeh, Iracheta-Vellve, Arvin, Hamel, Keith M., Olander, Kira E., Davis, Thomas G. R., McGuire, Kathleen A., Halvorsen, Geoff T., Avila, Omar I., Patel, Chirag H., Kim, Sarah Y., Kammula, Ashwin V., Muscato, Audrey J., Halliwill, Kyle, Geda, Prasanthi, Klinge, Kelly L., Xiong, Zhaoming, Duggan, Ryan, Mu, Liang, Yeary, Mitchell D., Patti, James C., Balon, Tyler M., Mathew, Rebecca, Backus, Carey, Kennedy, Domenick E., Chen, Angeline, Longenecker, Kenton, Klahn, Joseph T., Hrusch, Cara L., Krishnan, Navasona, Hutchins, Charles W., Dunning, Jax P., Bulic, Marinka, Tiwari, Payal, Colvin, Kayla J., Chuong, Cun Lan, Kohnle, Ian C., Rees, Matthew G., Boghossian, Andrew, Ronan, Melissa, Roth, Jennifer A., Wu, Meng-Ju, Suermondt, Juliette S. M. T., Knudsen, Nelson H., Cheruiyot, Collins K., Sen, Debattama R., Griffin, Gabriel K., Golub, Todd R., El-Bardeesy, Nabeel, Decker, Joshua H., Yang, Yi, Guffroy, Magali, Fossey, Stacey, Trusk, Patricia, Sun, Im-Meng, Liu, Yue, Qiu, Wei, Sun, Qi, Paddock, Marcia N., Farney, Elliot P., Matulenko, Mark A., Beauregard, Clay, Frost, Jennifer M., Yates, Kathleen B., Kym, Philip R., Manguso, Robert T.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 26.10.2023; Nature Publishing Group
• Subjects: 101/58; 13/1; 13/106; 13/21; 13/31; 13/51; 14; 14/34; 38/39; 38/91; 42/41; 59/5; 60 APPLIED LIFE SCIENCES; 631/67/1059/2325; 631/67/580; 64/60; 692/308/2778; 96/1; 96/31; Animal models; Animals; Antibodies; Antigens; Bioavailability; Cancer; Cancer immunotherapy; CD8 antigen; CD8-Positive T-Lymphocytes - drug effects; CD8-Positive T-Lymphocytes - immunology; Cell culture; Cell growth; Clonal deletion; Design; Disease Models, Animal; Drug dosages; Drug Resistance, Neoplasm; Humanities and Social Sciences; Humans; Immune Checkpoint Inhibitors; Immune system; Immunity; Immunotherapy; Immunotherapy - methods; Inhibitors; Interferons - immunology; Killer Cells, Natural - drug effects; Killer Cells, Natural - immunology; Kinases; Lymphocytes; Lymphocytes T; Mice; multidisciplinary; Naphthalenes - pharmacology; Natural killer cells; Neoplasms - drug therapy; Neoplasms - enzymology; Neoplasms - immunology; Patients; PD-1 protein; Phosphatase; Phosphorylation; Plasma; preclinical research; Protein Tyrosine Phosphatase, Non-Receptor Type 1 - antagonists & inhibitors; Protein Tyrosine Phosphatase, Non-Receptor Type 2 - antagonists & inhibitors; Proteins; PTPN2 protein; Science; Science (multidisciplinary); Signal transduction; Solid tumors; T cell receptors; Therapeutic targets; Thiadiazoles - pharmacology; Tumor microenvironment; Tumor Microenvironment - drug effects; Tumor Microenvironment - immunology; Tumors; tumour immunology; Tyrosine

Immune checkpoint blockade is effective for some patients with cancer, but most are refractory to current immunotherapies and new approaches are needed to overcome resistance 1 , 2 . The protein tyrosine phosphatases PTPN2 and PTPN1 are central regulators of inflammation, and their genetic deletion...