Pediatric Immuno-Oncology
Our research group uses functional genomics and advanced genetic engineering to elucidate the interactions of immune cells with cancer cells and improve immunotherapy of solid tumors.
In recent years, chimeric antigen receptor (CAR) T cells have revolutionized the treatment of hematological malignancies. However, CAR T cells are still ineffective in most solid tumors. Solid tumors represent particularly challenging targets for cancer immunotherapy because they are heterogeneous and establish a microenvironment that can suppress T cell responses.
We have recently developed CRISPR-based Modular Pooled Knockin Screens to study which (synthetic or natural) gene products can be overexpressed in primary human T cells to enhance the efficacy and fitness of CARs (Blaeschke et al., Cell, 2023).
Our research at KiTZ and DKFZ focuses on the immunotherapy of brain tumors and combines a variety of different tools such as CRISPR screens, syngeneic and xenograft models, spatial technologies, immune cell engineering and functional analyses. All of our projects are performed in close collaboration with our colleagues at KiTZ, DKFZ and UKHD, but also with national and international partners.
Together, we aim to decode immune cell functionality in the context of solid tumors and engineer the next generation of immunotherapies for cancer treatment.
Blaeschke, F., Chen, Y., Apathy, R., Daniel, B., Chen, A.Y., Chen, P., Sandor, K., Zhang, W., Li, Z., Mowery, C.T., Yamamoto, T.N., Nyberg, W.A., To, A., Yu, R., Bueno, R., Kim, M., Schmidt, R., Goodman, D.B., Feuchtinger, T., Eyquem, J., Ye, C.J., Carnevale, J., Satpathy, A.T., Shifrut, E., Roth, T.L., and Marson, A. (2023). Modular Pooled Discovery of Synthetic Knockin Sequences to Program Durable Cell Therapies. Cell 186, 4216-4234 e4233.
Carnevale, J., Shifrut, E., Kale, N., Nyberg, W.A., Blaeschke, F., Chen, Y.Y., Li, Z., Bapat, S.P., Diolaiti, M.E., O'leary, P., Vedova, S., Belk, J., Daniel, B., Roth, T.L., Bachl, S., Anido, A.A., Prinzing, B., Ibanez-Vega, J., Lange, S., Haydar, D., Luetke-Eversloh, M., Born-Bony, M., Hegde, B., Kogan, S., Feuchtinger, T., Okada, H., Satpathy, A.T., Shannon, K., Gottschalk, S., Eyquem, J., Krenciute, G., Ashworth, A., and Marson, A. (2022). RASA2 ablation in T cells boosts antigen sensitivity and long-term function. Nature 609, 174-182.
Schmidt, R., Steinhart, Z., Layeghi, M., Freimer, J.W., Bueno, R., Nguyen, V.Q., Blaeschke, F., Ye, C.J., and Marson, A. (2022). CRISPR activation and interference screens decode stimulation responses in primary human T cells. Science 375, eabj4008
Blaeschke, F., Stenger, D., Apfelbeck, A., Cadilha, B.L., Benmebarek, M.R., Mahdawi, J., Ortner, E., Lepenies, M., Habjan, N., Rataj, F., Willier, S., Kaeuferle, T., Majzner, R.G., Busch, D.H., Kobold, S., and Feuchtinger, T. (2021). Augmenting anti-CD19 and anti-CD22 CAR T-cell function using PD-1-CD28 checkpoint fusion proteins. Blood Cancer J 11, 108.