Image-guided tumour therapies with CAR T cells co-engineered for local depletion of immunosuppressive macrophages

Principal investigator: Claudia Rössig
Project number: CRC 1450 A07
Project term: 01/2025–12/2028

We aim to enable effective T cell targeting of solid cancers by co-engineering T cells with tumour-antigen specific CARs and for local release of an antagonist that selectively depletes immunosuppressive myeloid cell populations in tumour tissues. Our multimodal cellular targeting and imaging strategy will include in vivo tracking of the inflammatory tumour microenvironment, the fate of the CAR T cells and released antagonist along with local tumour growth and dissemination. The insights from this project will inform clinical translation of this novel strategy.

Schematic of image guided tumour therapies with a novel GD2-specific CAR T cell micropharmacy. An orthotopic xenograft model will be established based on coinjection of human tumour cells along with human monocytes into severely immunodeficient NOD scid gamma (NSG) mice, followed by therapeutic intervention with either the therapeutic antibody emactuzumab in combination with GD2CAR T cells or with GD2CAR T cells secreting CSF1R scFv. In addition to standard BLI monitoring of tumour growth, the CSF1R scFv will be tracked by [68Ga]-labelled nanobodies against the ALFA-tag, and the inflammatory TME will be visualized with [18F]FDG-PET-MRI or [64Cu]-CD206 antibody-PET-MRI.
© CRC inSight A07

Team

Principal investigator

Project member

Fischer-Riepe, Lena, Dr. rer. nat.
Department of Pediatric Hematology and Oncology

Publications

The names of the principal investigators in our network have been bolded. Publications released prior to 2025, when funding for the project commenced, represent previous project-related work.

2024

Fischer-Riepe L, Kailayangiri S, Zimmermann K, Pfeifer R, Aigner M, Altvater B, Kretschmann S, Völkl S, Hartley J, Dreger C, Petry K, Bosio A, von Döllen A, Hartmann W, Lode H, Görlich D, Mackensen A, Jungblut M, Schambach A, Abken H, Rossig C. Preclinical Development of CAR T Cells with Antigen-Inducible IL18 Enforcement to Treat GD2-Positive Solid Cancers. Clin Cancer Res 2024;30: 3564-3577. Abstract

2022

Holterhus M, Altvater B, Kailayangiri S, Rossig C. The Cellular Tumor Immune Microenvironment of Childhood Solid Cancers: Informing More Effective Immunotherapies. Cancers (Basel) 2022;14Abstract

2020

Zimmermann K, Kuehle J, Dragon AC, Galla M, Kloth C, Rudek LS, Sandalcioglu IE, Neyazi B, Moritz T, Meyer J, Rossig C, Altvater B, Eiz-Vesper B, Morgan MA, Abken H, Schambach A. Design and Characterization of an "All-in-One" Lentiviral Vector System Combining Constitutive Anti-G(D2) CAR Expression and Inducible Cytokines. Cancers (Basel) 2020;12Abstract