Address
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Themen
Research
- Focus A
- A01: Targeting tumor cell network communication to overcome primary and adaptive resistance in glioblastoma
- A02: Development of a specific combination therapy for histone H3-mutant pediatric glioblastoma
- A03: Deciphering resistance against targeted treatments
- A04: Elucidating tumor-associated microglia interactions in astrocytomas CNS WHO-grade 4
- A05: Predictive biomarkers for MGMT-promoter-methylated glioblastoma (2019 – 2023)
- A06: Resistance mechanisms of glioblastoma against alkylating agents and radiotherapy
- A07: Mapping and targeting neuron-tumor networks to tackle therapy resistance in glioblastoma
- A08: Personalized glioblastoma treatment guided by patient-derived tumor organoids
Research
- Focus B
- B01: Mechanisms of response and resistance to glioma-specific t cells
- B02: DNA mis-match repair regulates immune checkpoint blockade therapy in glioblastoma (2019 – 2023)
- B03: Targeting immunosuppressive programs in isocitrate dehydrogenase mutant gliomas
- B04: Impact of myeloid cells on the adaptive immune response in newly diagnosed and recurrent glioblastomas
- B05: Dissecting the response of glioblastoma and its tumor microenvironment to focused high-dose radiotherapy (2019 – 2023)
- B06: Visualization and characterization of immune responses in H3K27M mutant gliomas
Research
- Focus C
- C01: Comprehensive preclinical pharmacology testing of drugs used for glioblastoma treatment
- C02: Radiomics, radiogenomics and deep-learning in neurooncology
- C03: Imaging immune signatures of glioma response and resistance towards immunotherapy (2019 – 2023)
- C04: Metabolic signaling in glioblastoma: a spatial multi-omics approach
- C05: Overcoming glioma radio-resistance with particle therapy
- C06: Functional characterization of EGFR structural variants associated with long-term survival in glioblastoma, IDH-WT
Primary Mismatch Repair Deficient Glioma (PMMRDG), IDH-wildtype and H3-wildtype: A Giant Cell Tumor with Potential for Long-Term Survival Occurring at all Ages
RESEARCHResearch findings related to UNITE work packages A02/A03/A06/B01/B03/B04/C01/C06/
Replication-repair-deficiency is associated with increased risk of developing malignant gliomas. The aim of this study was to investigate primary mismatch repair deficient gliomas (PMMRDGs), a group of IDH-wildtype and H3-wildtype gliomas that is enriched among patients with CMMRD and Lynch syndrome. We investigated how PMMRDGs differ from other gliomas with respect to DNA methylation profile, genomic alterations, histopathology, and clinical outcomes. PMMRDGs occur in pediatric, adolescents and the elderly, falling in two related methylation clusters and are characterized by a high frequency of replication repair deficiency. Histology showed multinucleated giant cells, and immunohistochemistry demonstrated loss of MMR protein expression. Survival analysis revealed long-term survival in patients with high mutational burden (>50 mut/Mb) and an intact chromosome 9p region, which was validated in an independent reference cohort. Overall, our findings indicate that PMMRDGs represent a distinct type of IDH-wildtype gliomas with potential for long-term survival likely driven by immune activation
Link to Publication
Molecularly matched targeted therapies plus radiotherapy in glioblastoma: the phase 1/2a N2M2 umbrella trial
RESEARCHResearch findings related to UNITE work packages A01/A03/A06/B01/B04/C01/C02
Advances in molecular understanding and diagnostic precision of glioblastoma enable the identification of key genetic alterations in a timely manner and, in principle, allow treatments with targeted compounds based on molecular markers. Here we report the results of the phase 1/2 umbrella trial NCT Neuro Master Match (N2M2), which evaluated targeted treatments in 228 patients with newly diagnosed glioblastoma without O6-methylguanine DNA-methyltransferase promoter hypermethylation. Stratification for treatment was conducted by a trial-specific molecular tumor board across five subtrials, each evaluating a targeted therapy—alectinib, idasanutlin, palbociclib, vismodegib or temsirolimus—selected according to the best-matching molecular alteration. Patients without matching alterations were randomized between subtrials without strong biomarkers using atezolizumab and asunercept, and the standard of care (SOC), temozolomide. All received radiotherapy. The primary endpoints were dose-limiting toxicities (phase 1) and progression-free survival at 6 months (PFS-6; phase 2). Secondary endpoints included safety and tolerability, as well as overall survival (OS). The subtrials for alectinib and vismodegib did not open as they did not have matching patients. The idasanutlin subtrial (n = 9) was terminated early at the discretion of the manufacturing company. The temsirolimus subtrial (n = 46) demonstrated a PFS-6 of 39.1% and median OS of 15.4 months in patients with activated mammalian target of rapamycin (mTOR) signaling compared to a PFS-6 at 18.5% in the SOC group (n = 54), meeting the primary endpoint. The atezolizumab (n = 42), asunercept (n = 26) and palbociclib (n = 41) subtrials did not meet the primary endpoint for efficacy. The safety signals of N2M2 match prior experiences with the drugs in quality and quantity; no relevant negative interaction with the parallel radiotherapy was noted. The results of the N2M2 trial support further investigation of temsirolimus in addition to radiotherapy in patients with newly diagnosed glioblastoma with activated mTOR signaling.
Link to Publication
Vaccine-induced T cell receptor T cell therapy targeting a glioblastoma stemness antigen
RESEARCHResearch findings related to UNITE work packages A03/B01/B03
T cell receptor-engineered T cells (TCR-T) could be advantageous in glioblastoma by allowing safe and ubiquitous targeting of the glioblastoma-derived peptidome. Protein tyrosine phosphatase receptor type Z1 (PTPRZ1), is a clinically targetable glioblastoma antigen associated with glioblastoma cell stemness. Here, we identify a therapeutic HLA-A*02-restricted PTPRZ1-reactive TCR retrieved from a vaccinated glioblastoma patient. Single-cell sequencing of primary brain tumors shows PTPRZ1 overexpression in malignant cells, especially in glioblastoma stem cells (GSCs) and astrocyte-like cells. The validated vaccine-induced TCR recognizes the endogenously processed antigen without off-target cross-reactivity. PTPRZ1-specific TCR-T (PTPRZ1-TCR-T) kill target cells antigen-specifically, and in murine experimental brain tumors, their combined intravenous and intracerebroventricular administration is efficacious. PTPRZ1-TCR-T maintain stem cell memory phenotype in vitro and in vivo and lyse all examined HLA-A*02+ primary glioblastoma cell lines with a preference for GSCs and astrocyte-like cells. In summary, we demonstrate the proof of principle to employ TCR-T to treat glioblastoma.
Link to Publication
Characterizing and targeting glioblastoma neuron-tumor networks with retrograde tracing
RESEARCHResearch findings related to UNITE work packages A06/A07/B06N
Glioblastomas are invasive brain tumors with high therapeutic resistance. Neuron-to-glioma synapses have been shown to promote glioblastoma progression. However, a characterization of tumor-connected neurons has been hampered by a lack of technologies. Here, we adapted retrograde tracing using rabies viruses to investigate and manipulate neuron-tumor networks. Glioblastoma rapidly integrated into neural circuits across the brain, engaging in widespread functional communication, with cholinergic neurons driving glioblastoma invasion. We uncovered patient-specific and tumor-cell-state-dependent differences in synaptogenic gene expression associated with neuron-tumor connectivity and subsequent invasiveness. Importantly, radiotherapy enhanced neuron-tumor connectivity by increased neuronal activity. In turn, simultaneous neuronal activity inhibition and radiotherapy showed increased therapeutic effects, indicative of a role for neuron-to-glioma synapses in contributing to therapeutic resistance. Lastly, rabies-mediated genetic ablation of tumor-connected neurons halted glioblastoma progression, offering a viral strategy to tackle glioblastoma. Together, this study provides a framework to comprehensively characterize neuron-tumor networks and target glioblastoma.
Link to Publication
Research Grant to advance Imaging‑Driven Glioblastoma Treatment
CAREERSJonas Scheck (B06N) is the recipient of a research grant by the Family Mehdorn Foundation. The funded project brings together researchers from UT MD Anderson, the German Cancer Research Center (DKFZ), and University Hospital Heidelberg (UKHD). Building on recently developed imaging platforms, the team aims to further advance drug‑delivery strategies for glioblastoma, with the goal of improving therapeutic precision for the highly aggressive brain tumor.
Outstanding Achievements Recognized with Thomas and Doris Ammann Prize
CAREERSStefan Pfister (C01) has been awarded the Thomas and Doris Ammann Prize. His research has uncovered multiple previously unrecognized genetic alterations that drive the development of various pediatric brain tumor types. These include mutations that reveal new therapeutic targets, as well as genetic changes that point to an inherited predisposition to cancer. Together, these discoveries have substantially deepened the understanding of the biological mechanisms underlying childhood brain tumors and have paved the way for more precise, individually tailored treatment approaches.
In previous years, his exceptional scientific contributions have also been recognized with several prestigious honors, including the German Cancer Award (2013), the Léopold Griffuel Award (2021), the Baden‑Württemberg State Research Award (2022), and the Gottfried Wilhelm Leibniz Prize of the German Research Foundation (2023).
Distinguished Achievement: MTZ Award for Systems Medicine 2026
CAREERSDirk Hoffmann (A03) has been awarded the MTZ Award for Systems Medicine 2026 in recognition of his outstanding research on malignant brain tumors. His work provides important impulses for the development of novel therapeutic strategies against glioblastomas. His research focuses on the molecular and cellular mechanisms of glioblastoma, with particular emphasis on tumor heterogeneity, therapy resistance, and the identification of new biomarkers and targeted therapeutic approaches. During his doctoral studies, he investigated the communication and oncogenic properties of glioblastoma cells that are interconnected through tumor microtubes—an essential mechanism underlying therapy resistance. By combining single-cell–resolved and bulk multi‑omics analyses, he deciphered the molecular profile of these cellular networks and derived a network signature that was validated as a prognostic biomarker across several independent patient cohorts and is currently being evaluated in prospective clinical studies. In addition, his research is closely integrated with clinical trials on molecularly targeted therapeutic strategies, in which he identifies and validates prognostic and predictive biomarkers through retrospective multi‑omics analyses.
The MTZ Award for Systems Medicine, presented by the independent MTZ Foundation under the patronage of the Federal Ministry for Research, Technology and Space (BMFTR), is among the most prestigious German early‑career awards in medical systems biology and systems medicine. It honors exceptional dissertations that apply interdisciplinary approaches to investigate complex biological systems using molecular‑genetic, clinical, mathematical, or computational methods.
Dirk Hoffmann is also the recipient of the Richtzenhain Doctoral Prize (2025), in recognition of his outstanding doctoral thesis.
Honoring Exceptional Advances in Molecular Neuro‑Oncology: German Cancer Prize 2026
CAREERSFelix Sahm (A06) is one of the recipients of the German Cancer Prize in the Translational Research Category. The Prize is awarded annually by the German Cancer Society and the German Cancer Foundation and is considered one of the highest distinctions in oncology. Sahm is recognized for his leading contributions to the molecular classification of brain tumors, particularly through the development of integrated diagnostic frameworks that combine DNA methylation profiling, genomic alterations, and computational analysis. These classification systems have substantially improved diagnostic accuracy across tumor entities, refined prognostic stratification, and enabled more biologically informed therapeutic decision‑making.
Felix Sahm’s other scientific awards include the EANO Research Award (2025) and the Paul-Kleihues-Prize (2013).
NEWSLETTER 06/2026
NEWSLETTERDear Members and Friends of UNITE,
We are happy to share recent highlights, including a recap of our retreats, seminar series and the latest updates from research. This edition also features a curated overview of upcoming UNITE events and Travel grants, alongside short introductions to the newest members of the UNITE staff.
We hope you enjoy reading the latest news and look forward to the continued progress we’ll achieve together!
Best wishes,
UNITE Project Management Team
UNITE _Newsletter_ 6
NEWSLETTER 04/2025
NEWSLETTERDear Members and Friends of UNITE,
We are happy to share recent highlights, including a recap of our seminars, the UNITE & Fellow Retreat, and the
latest updates from our team. In this edition, we also invite you to apply for the upcoming travel grants, provide an
overview of upcoming workshops and UNITE events, and introduce new members of the UNITE staff.
We hope you enjoy reading the latest news and look forward to the continued progress we’ll achieve together!
Best wishes,
The UNITE Project Management Team
UNITE_Newsletter_4