📋 Tender Overview
Senolytic Car T Cells As Novel Therapeutic Concept For Solid Tumors And Senescence-Associated Diseases.
New Immunotherapies For Cancer And Beyondchimeric Antigen Receptor (Car) T Cells Are Genetically Engineered Immune Cells That Destroy Target Cells With Precision Thanks To Combined Antigen Binding And T Cell Activating Functions. Their Adaptation Has Enabled New Treatments In Patients With Haematological B Cell Malignancies. They Are Very Promising For Other Cancer Types And Diseases, Such As Senescence-Associated Pathologies, But Limitations From The Antigenic Heterogeneity Or Impaired T Cell Trafficking Must Be Solved. The Eu-Funded Carsen Project Will Develop A Novel Therapeutic Concept Through The Engineering Of T Cells Against Senescent Cells That Will Be Combined With Therapies That Induce Senescence In Tumour Cells. The New Therapy Will Be Tested For Safety And Efficacy In Murine Models Of Cellular Senescence And Solid Tumours.
Funded Under
Excellent Science - European Research Council (Erc)
Total Cost
€ 1 818 637,50
Eu Contribution
€ 1 818 637,00
Coordinated By
Eberhard Karls Universitaet Tuebingen
Germany
Start Date
1 January 2022
End Date
31 December 2026
Objective
The adoptive transfer of T cells expressing CD19-directed chimeric antigen receptors (CARs) has yielded remarkable efficacy in patients with hematological B-cell malignancies. CARs are a class of synthetic receptors that reprogram T cell specificity, function and metabolism. Engineered T cells are applicable in principle to other cancers and diseases, but clinical success will critically depend on further progress to overcome current limitations such as antigenic heterogeneity or impaired T cell trafficking and function. We propose to develop CAR T cells targeting senescent cells as a novel therapeutic concept for cancer and senescence-associated diseases. Cellular senescence is a stress-response program characterized by stable cell cycle arrest that serves as a potent tumor-suppressive mechanism. Conversely, accumulation of senescent cells generates a chronic inflammatory milieu, which contributes to a plethora of pathologies, such as liver or lung fibrosis and can even promote tumor progression.
Our preliminary data demonstrate that CAR T cells can efficiently clear senescent cells, providing therapeutic benefit in a murine model of liver fibrosis. We thus firmly believe that senolytic CAR T cells have broad therapeutic potential. To this end, we will apply innovative engineering strategies to develop modular CAR designs tailored to senescence-specific requirements. We will determine safety and efficacy of senolytic CAR T cells in murine models of cellular senescence and solid tumors. Importantly, we will evaluate combined treatment approaches of senescence-inducing therapies with CAR T cells targeting senescent and proliferating tumor cells. Finally, we will investigate engineering tools to optimally direct senolytic CAR activity to mediate durable t
