Enhancing the Immune System

Our research focuses on the rational design and functional enhancement of CAR T cell products to achieve superior efficacy, both in solid tumors and in hematological malignancies. Building upon our proprietary anti-GD2 platform, we are engineering novel CAR constructs with optimized intracellular signaling domains and integrated functional modules to enhance T cell activation, persistence, and resistance to tumor-induced immunosuppression.To rigorously evaluate these strategies, we have established a comprehensive and highly translational preclinical pipeline. This includes advanced 2D and 3D culture systems that recapitulate tumor complexity, incorporating stromal and healthy tissue components, as well as patient-derived primary tumor models obtained through close clinical collaborations. Our expertise in primary cell isolation and stabilization enables the generation of clinically relevant models. Using live imaging and multiplex platforms, we monitor CAR T cell dynamics in real time, capturing activation, cytotoxicity, and cytokine release. We also conduct comprehensive safety profile assessments to ensure translational relevance and clinical applicability of our therapeutic strategies. These studies are complemented by a broad portfolio of in vivo models, both orthotopic and heterotopic, covering neuroblastoma, glioblastoma, skin cancers, sarcomas, and T-cell acute lymphoblastic leukemia. 

A core strength of the Unit lies in its advanced plasmid-based platforms for gene therapy, enabling the rapid design and generation of lentiviral and retroviral vectors for innovative CAR constructs. We possess extensive expertise in vector engineering, supporting the development of next-generation receptors with enhanced functionality and modular design. Our approach integrates both intrinsic and extrinsic engineering strategies. We refine intracellular signaling domains to precisely tune CAR activation, persistence, and effector functions, while in parallel developing complementary receptor architectures that operate alongside the CAR. These systems provide additional functional modules that enhance T cell performance within hostile tumor microenvironments, addressing key challenges such as antigen heterogeneity, limited infiltration, and immunosuppression. In parallel, we actively pursue the identification and validation of novel tumor-associated targets, expanding the spectrum of actionable antigens in solid tumors. These efforts are tightly integrated with our engineering platforms, enabling the rapid translation of newly identified targets into functional CAR designs. By combining modular engineering, parallel receptor systems, and target discovery, our platform supports rapid iteration and validation of innovative constructs, accelerating the transition from concept to preclinical proof-of-principle and ultimately improving therapeutic efficacy.

The CAR T Unit is strongly committed to bridging the gap between preclinical innovation and clinical application. Our translational efforts are focused on the development of robust, GMP-compliant manufacturing processes to enable the clinical deployment of our CAR T products. This includes the systematic selection and validation of clinical-grade reagents and culture conditions, as well as the development and testing of GMP-compliant lentiviral vectors. In collaboration with the Center for Advanced Cell Therapy (ACT) in Oslo, directed by Prof. Anna Pasetto, https://www.ous-research.no/act we are conducting dedicated manufacturing runs to optimize scalability, standardization, and regulatory compliance. These activities are integral to our technology transfer strategy, ensuring that our CAR T platforms can be efficiently translated into clinical-grade products. Through this integrated approach, the Unit aims to accelerate the advancement of novel CAR T therapies into early-phase clinical trials and ultimately improve patient outcomes.