BRAIN TUMOR AND IMMUNE CELL ENGINEERING
Tumors arising in the brain are notoriously hard to treat. Intensive research in the last decade provided in depth characterization of the molecular profile of high grade gliomas, but unfortunately no impactful novel therapies. We contributed to immune based therapies for gliomas, especially in the identification of overexpressed cell surface markers of GBM in vivo and with the development multiepitopic vaccinations using synthetic peptides. We had the opportunity to translate our research into the clinic in an early phase trial where 19 patients with newly diagnosed GBM tumors were treated with the IMA950 peptide vaccine. We were able to demonstrate safety and immunogenicity. This endeavour led to another ambitious phase I trial using a personalized vaccination approach adapted to each patient’s tumor molecular profile.
Our next endeavour is to develop improved chimeric antigen receptor (CAR)-T cell approaches for glioma for the development of successful translational programs. T-cell engineering allows the construction of cell products harboring a high-affinity single-chain fragment variable (scFv) specific for a target of interest, fused to domains necessary for full activation and costimulation. CAR-T cell therapy in the context of brain tumors is promising because glioma is a good example of how specific improvements in trafficking, persistence, and resistance to the immunosuppressive factors related to the TME will be especially critical for success of engineered cellular therapies. We are fortunate to benefit from the generous support of the ISREC Foundation and to be part of the newly formed Swiss Cancer Center Léman (SCCL) which brings together fundamental, translational and clinical cancer research experts from Geneva and Lausanne. The SCCL federates skills and ressources at the cutting edge of the fight against cancer and allows us to integrate our efforts in a wide multidisciplinary community.
Expertise:
- Neuro oncology
- Immunotherapy
- Oncoimmunology
- CAR-T cell therapies
- Synthetic biology
Selected publications:
1. Pittet M., Michielin O., and Migliorini D. Clinical relevance of tumour-associated macrophages. Nature Reviews Clinical Oncology 2022 Jun;19(6):402-421.
2. Wenes M, Jaccard A, Wyss T, Maldonado-Pérez N, Thing Teoh S, Lepez A, Renaud F, Franco F, Waridel P, Vuillefroy de Silly C, Tschumi B, Dumauthioz N, Zhang L, Donda A, Martin F, Migliorini D, Lunt S Y, Ho PC, Romero P. The mitochondrial pyruvate carrier regulates memory T cell differentiation and antitumor function. Cell Metabolism 2022 May 3;34(5):731-746.e9.
3. Parker K.R.*, Migliorini D.*#, Perkey E., Yost K.Y., Bhaduri A., Bagga P., Haris M., Wilson N.E., Liu F., Gabunia K., Scholler J., Montine T.J., Bhoj V.G., Reddy R., Mohan S., Maillard I., Kriegstein A.R., June C.H., Chang H.Y, Posey A.D. Jr., Satpathy A.T.#. Single-cell analyses identify brain mural cells expressing CD19 as potential off-tumor targets for CAR-T immunotherapies. Cell 2020 DOI: doi:10.1016/j.cell.2020.08.022.
*contributed equally #co-corresponding.
4. Migliorini D., Dutoit V., Allard M., Grandjean Hallez N., Marinari E., ..., Momjian S., Lobrinus A., Merkler D., Vargas M-I., Walker P.R., Patrikidou A., and Dietrich P-Y. Phase I/II trial testing safety and immunogenicity of the multipeptide IMA950/poly-ICLC vaccine in newly diagnosed adult malignant astrocytoma patients. Neuro Oncology 2019 Feb 12. doi:10.1093/neuonc/noz040.
5. Hilf N., Kuttruff-Coqui S., Frenzel K.,.., von Deimling A., Migliorini D., Kroep S.,.., Sahin U., Dietrich P-Y, Wick W. Actively personalized vaccination in newly diagnosed glioblastoma. Nature. 2019 Jan;565(7738):240-245.
10 Mar 2023