Janda group

Group leader: Dr. Claudia Janda

“Our research is driven by the vision to use our expertise in protein engineering to interrogate questions in pediatric oncology from a new angle and to develop next-generation biologics and immunotherapies for cancer therapy." Claudia Janda - Group leader

Developing antibodies and nanobodies for theranostics

By combining therapy and diagnostics (theranostics) we hope to improve personalized treatment for pediatric oncology. Theranostics with antibody-based radiotracers for PET imaging and radioimmunotherapy have become important tools for diagnosis, treatment, treatment stratification to immunotherapies, and treatment monitoring in adult oncology. However, they remain largely unexplored in pediatric oncology despite great opportunities. In collaboration with Prof. Dr. Max van Noesel and the Theranostics Facility of the UMC Utrecht, we develop nanobody-based radiotracers for PET imaging and radioimmunotherapy targeting antigens overexpressed on osteosarcoma, and other pediatric solid tumors. Ultimately, we aim to improve treatment and use target-specific PET imaging for therapy evaluation in children with sarcomas.

Engineering chimeric antigen receptors and bispecific T cell engagers for immunotherapies

Cancer immunotherapies aim to stimulate the patient’s immune system to combat cancer and hold great promise for treating cancers that are refractory to standard treatment. However, osteosarcoma and other pediatric solid tumors pose unique challenges for immunotherapies, such as low expression of tumor-specific antigens, antigen escape, dense packing of the extracellular matrix, and immunosuppressive microenvironment.
 
In collaboration with the CAR T Cell Program, the Cell Therapy Facility, and the Single Cell Genomics Facility of the Princess Máxima Center, we develop antibodies and nanobodies for (newly identified) pediatric tumor antigens and use innovative screening approaches to interrogate the structure-function relationship of chimeric antigen receptors and bi-specific T cell engagers.

Engineering modulators of the Wnt and BMP signaling pathway to enhance tissue regeneration after therapy-induced damage

Wnt and BMP signaling are conserved developmental signaling pathways activated by promiscuous interactions between multiple ligand and receptor variants, allowing them to elicit highly pleiotropic functions. Owing to the critical roles of both pathways in the maintenance, proliferation, and differentiation of stem cells, the specific activation or inhibition of signaling has attracted much interest in regenerative medicine. 
 
Our lab has a long-standing interest in combining structural and functional studies and protein and antibody engineering approaches to develop Wnt and BMP signaling modulators with drug-like properties to stimulate the regeneration and repair of damaged tissue specifically. Our current interest is in developing novel Wnt surrogates that enhance regeneration after therapy-induced tissue damage, for instance, the radiation-induced damage of the intestine and chemotherapy-induced ototoxicity affecting hearing and balance. We interrogate the activity of these Wnt surrogates in various in vitro and in vivo tissue injury and regeneration models. 

Identifying new therapeutic strategies for high-risk osteosarcoma

Osteosarcoma is the most common type of malignant bone tumor, accounting for 5% of all pediatric tumors. Osteosarcoma predominantly affects children and young adults and most frequently develops around the metaphysis of long bones. While children with localized osteosarcoma have improved outcomes, children with metastatic and recurrent disease respond poorly to standard therapies and have 5-year survival rates of <30%. Therefore, there is an ongoing need for more selective and effective therapeutics.
 
To improve our understanding of osteosarcoma development and progression, we closely collaborate with various groups at the Princess Máxima Center. Together we take a multidisciplinary approach using state-of-the-art technologies, such as single-cell transcriptomics,  single-cell genomics, and organoid technology, with the ultimate goal of identifying new therapeutic strategies for children with high-risk osteosarcoma.