Pinkert, Jessica and Boehm, Hans-Henning and Trautwein, Mark and Doecke, Wolf-Dietrich and Wessel, Florian and Ge, Yingzi and Gutierrez, Eva Maria and Carretero, Rafael and Freiberg, Christoph and Gritzan, Uwe and Luetke-Eversloh, Merlin and Golfier, Sven and Von Ahsen, Oliver and Volpin, Valentina and Sorrentino, Antonio and Rathinasamy, Anchana and Xydia, Maria and Lohmayer, Robert and Sax, Julian and Nur-Menevse, Ayse and Hussein, Abir and Stamova, Slava and Beckmann, Georg and Glueck, Julian Marius and Schoenfeld, Dorian and Weiske, Joerg and Zopf, Dieter and Offringa, Rienk and Kreft, Bertolt and Beckhove, Philipp and Willuda, Joerg (2022) T cell-mediated elimination of cancer cells by blocking CEACAM6-CEACAM1 interaction. ONCOIMMUNOLOGY, 11 (1): 2008110. ISSN 2162-402X,
Full text not available from this repository. (Request a copy)Abstract
Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6), a cell surface receptor, is expressed on normal epithelial tissue and highly expressed in cancers of high unmet medical need, such as non-small cell lung, pancreatic, and colorectal cancer. CEACAM receptors undergo homo- and heterophilic interactions thereby regulating normal tissue homeostasis and angiogenesis, and in cancer, tumor invasion and metastasis. CEACAM6 expression on malignant plasma cells inhibits antitumor activity of T cells, and we hypothesize a similar function on epithelial cancer cells. The interactions between CEACAM6 and its suggested partner CEACAM1 on T cells were studied. A humanized CEACAM6-blocking antibody, BAY 1834942, was developed and characterized for its immunomodulating effects in co-culture experiments with T cells and solid cancer cells and in comparison to antibodies targeting the immune checkpoints programmed cell death protein 1 (PD-1), programmed death-ligand 1 (PD-L1), and T cell immunoglobulin mucin-3 (TIM-3). The immunosuppressive activity of CEACAM6 was mediated by binding to CEACAM1 expressed by activated tumor-specific T cells. BAY 1834942 increased cytokine secretion by T cells and T cell-mediated killing of cancer cells. The in vitro efficacy of BAY 1834942 correlated with the degree of CEACAM6 expression on cancer cells, suggesting potential in guiding patient selection. BAY 1834942 was equally or more efficacious compared to blockade of PD-L1, and at least an additive efficacy was observed in combination with anti-PD-1 or anti-TIM-3 antibodies, suggesting an efficacy independent of the PD-1/PD-L1 axis. In summary, CEACAM6 blockade by BAY 1834942 reactivates the antitumor response of T cells. This warrants clinical evaluation.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ADHESION MOLECULE; COLORECTAL-CANCER; CEA FAMILY; ANTIGEN; EXPRESSION; CEACAM6; MEMBERS; PROGRESSION; MECHANISMS; PROTEINS; CEACAM6; immune checkpoint inhibitor; humanized antibody; T cell; immune response; elimination of cancer cells |
| Subjects: | 500 Science > 530 Physics 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) Medicine > Zentren des Universitätsklinikums Regensburg > Regensburger Centrum für Interventionelle Immunologie (RCI) Physics > Institute of Theroretical Physics |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Feb 2024 06:21 |
| Last Modified: | 14 Feb 2024 06:21 |
| URI: | https://pred.uni-regensburg.de/id/eprint/57183 |
Actions (login required)
 |
View Item |
