DKTK Freiburg Scientific Community Meeting

Jul 7, 2025, 12:00 PM → Jul 8, 2025, 5:00 PM Europe/Berlin

Plenum 110 (Caritas Tagungszentrum Freiburg)

Anja Hernández (Deutsches Krebsforschungszentrum), Melanie Börries (Institute of Medical Bioinformatics and Systems Medicine, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Partner Site Freiburg), Rhena Klar (Deutsches Krebsforschungszentrum)

DKTK Freiburg Scientific Community Meeting 2025

Date: July 7–8, 2025
Venue: Caritas Conference Center, Wintererstraße 17–19, Freiburg

About the Meeting

The DKTK Freiburg Scientific Community Meeting 2025 will bring together researchers from across the DKTK Freiburg network to foster scientific exchange and collaboration. The meeting will focus on translational oncology research with a specific emphasis on the thematic areas defined in the DKTK Joint Funding 2025:

• Pillar 1: Therapeutic Innovations – Trial-enabling preclinical data packages and translational strategies toward early clinical development
• Pillar 2: Diagnostic Innovations & Molecular Prevention – Transfer-enabling or prospective study data packages supporting diagnostics, prevention, and reverse translation

 

PRELIMINARY PROGRAM (subject to change)

Monday, July 7, 2025

·       1:00–5:30 p.m. | Talks and Discussions

• 5:30–7:00 p.m. | Poster Session
• 7:00 p.m. | Dinner

Tuesday, July 8, 2025

·       10:30 a.m.–1:00 p.m. | Talks and Discussions

• 1:00 p.m. | Lunch
• 2:00–3:30 p.m. | Poster Session II
• 3:30–5:00 p.m. | Young Investigator Get-Together

Registration deadline: June 06^th, 2025

We are looking forward to your registration!

The Organizing Committee

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CHAIRS / PROGRAM COMMITTEE

Prof. Dr. Dr. Melanie Börries, DKTK Spokesperson Freiburg  

Prof. Dr. Robert Zeiser, Deputy DKTK Spokesperson Freiburg

 

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ABSTRACT SUBMISSION

Abstract submission for the DKTK Freiburg Scientific Community Meeting 2025 is now open!

We invite all members of the DKTK Freiburg community to submit abstracts for poster presentations and short talks. Contributions should align with the thematic areas of the DKTK Joint Funding 2025, particularly:

• Pillar 1: Therapeutic Innovations

• Pillar 2: Diagnostic Innovations & Molecular Prevention

 

🗓 Submission deadline: May 31st, 2025

We look forward to your contributions!

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VENUE

The Conference will take place in Caritas Conference Center, Wintererstraße 17–19, Freiburg.

Google: https://www.caritas-akademie.de/ueber-uns/ueber-uns

 

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Organizer:

Melanie Börries, IBSM Freiburg, DKTK Freiburg Spokesperson 

Anja Hernandez, DKTK Freiburg

Rhena Klar, DKTK Freiburg

on behalf of the DKTK Freiburg

 

 

Hosts: 

Melanie Börries, IBSM University Hospital Freiburg, DKTK Freiburg Spokesperson 

Robert Zeiser, Department of Medicine I, Univeristy Hospital Freiburg, Deputy DKTK Spokesperson Freiburg

 

 

 

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DKTK Freiburg 2025 sci-meeting_Program_final.pdf

DKTK Freiburg 2025 sci-meeting_Program.pdf

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DKTK Presentation-Template Freiburg-2.pptx

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Monday, July 7

12:00 PM → 1:00 PM Welcome Coffee

Networking Time

1:00 PM → 1:10 PM Welcome from Melanie Börries and Robert Zeiser

1:10 PM → 1:25 PM Pre-clinical therapeutic target identification for renal and bladder cancers

Clear cell renal cell carcinomas (ccRCC) are partly responsive to immune checkpoint inhibitor therapies that are based on inhibition of PD-1 and CTLA-4. We have described an autochthonous mouse model of ccRCC that is resistant to immune checkpoint inhibitor therapies and have identified numerous candidate immunosuppressive molecular pathways in ccRCC cells and in infiltrating myeloid lineage cells. Our ongoing work aims to systematically inhibit these pathways to identify the most promising approaches of improving anti-tumour immunity to guide the development of the next generation of immune-based ccRCC therapies.

Bladder urothelial carcinomas are characterised by recurrent mutations in several epigenetic tumour suppressor genes, highlighting that altered cellular epigenetics is a fundamental driver of these tumours. The UcarE Forschungsgruppe seeks to exploit epigenetic vulnerabilities of urothelial carcinomas though pharmacological and genetic screenings, genetic engineering of mouse and human cellular models and through pre-clinical testing of epigenetic drugs using human organoid and slice culture systems.

1:25 PM → 1:40 PM Spatiotemporally-Resolved Single-Cell Genomics Reveals Tumor Immune Escape Mechanisms in Glioblastoma

Our immune system possesses an intrinsic capability to recognize and eliminate malignant cells. Yet, tumors frequently subvert this defense by reprogramming tumor-infiltrating immune cells, driving immune evasion and contributing to therapy resistance. Single-cell genomics bear great potential to enhance our understanding of these processes by generating detailed molecular maps of immune cell states within the tumor microenvironment. However, the destructive nature of most single-cell genomics technologies inherently limits them to static snapshots, lacking the temporal resolution required for a causal understanding of tumor-immune interactions. To overcome this limitation, we developed a novel, temporally-resolved single-cell genomics platform that leverages fluorescent in vivo timestamping of circulating immune cells. Our methodology enables the time-resolved recording of transcriptional dynamics of an immune cell once it has been exposed to the tumor microenvironment and thereby offers the possibility to retrieve tumor-immune interactions in real-time. We extended this approach to single-cell resolved spatial transcriptomics, allowing dynamic tracking of immune cell infiltration into tumor niches across space and time. Applying this technology to a model for glioblastoma, we uncovered dynamic patterns of immune infiltration and adaptation, revealing a previously inaccessible perspective of tumor-immune interactions. Our spatiotemporal analyses identified reported drivers of immune escape in an unbiased, data-driven manner and suggested novel therapeutic vulnerabilities that could be exploited to reinvigorate anti-tumor immunity. Together, we present a novel space- and time-resolved single cell genomics technology with tremendous potential for the rational design of novel immunotherapies.

1:40 PM → 1:55 PM Translational Radioimmunotherapy

We previously demonstrated in preclinical and case reports that hypofractionated radiotherapy (RT) can induce tumor-specific T cells, thereby acting synergistically with immune checkpoint blockade (ICB), both locally and outside the RT field (abscopal effect). In the current funding period, we have (i) tested novel treatment combinations in mice to improve the abscopal effect, particularly T cell infiltration of abscopal tumors, e.g., by adding low-dose radiation or chemotherapy, which induce T cell-attracting chemokines; (ii) participated in clinical trials investigating the abscopal effect in metastatic melanoma/NSCLC (IRINA/PARADIGM DKTK-wide joint funding project and RadImmun-NSCLC with DKTK partners in Freiburg); (iii) investigated immune biomarkers in these and other trials. In the coming years, we aim to further improve RT/ICB combinations, particularly the abscopal effect, through additional adoptive T cell transfer, e.g., in ICB-resistant or poorly antigenic tumors. We started by adding TILs, TCR-transgenic T cells, or CD133-specific CAR T cells to RT/ICB in immunocompetent abscopal mouse models without lymphodepleting preconditioning. We are establishing methods to characterize and expand TILs from NSCLC tissue, and will assess their antitumor efficacy using patient-derived organoids (ongoing cooperation with Thoracic Surgery and FREEZE-O) and xenografts in mice +/- RT. In addition, TCR-engineered T cells will be produced. Collaborations on targeted radioligand therapy, preclinical MR and PET imaging to optimize combination therapies, and identification of neoepitopes using NGS/mass spectrometry are also planned. Our medium-term goal is to enable clinical trials using TILs or TCR-transgenic T cells to enhance the abscopal effect or for adoptive transfers with T cell-attracting RT.

1:55 PM → 2:10 PM Saturation mutational scanning uncovers druggability of all FGFR point mutations

Variants of unknown significance represent the biggest challenge for genomics-based precision oncology making high throughput functional genomics essential to characterize them. Aberrantly activated Fibroblast Growth Factor Receptors (FGFRs) frequently drive tumorigenesis across many tumor entities. Approved selective inhibitors (FGFRis) are available. However, it remains largely unknown which of the many different FGFR point mutations are druggable, i.e. activating signaling while not mediating resistance thereby substantially limiting the therapeutic potential of approved FGFRis.
We implemented a saturation mutational scanning platform to screen all 29259 possible point mutations in FGFR1-4. In positive selection screens of the kinase domains, we already identified 474 activating and 738 resistance-mediating mutations to the FGFRis pemigatinib or futibatinib yielding 301 druggable point mutations with a strong PS3/BS3 evidence level. Mutations in the same codon could strongly differ in their impact, underlining the necessity for a saturation approach. Importantly, our functional screens identified 97% of acquired resistance mutations in a clinical trial.
In summary, we provide a comprehensive and clinically highly relevant catalog of every single druggable point mutations in FGFR which is readily available for clinical decision support.
For the future, we see the necessity to expand our dataset to the regions outside of the kinase domain, to include the third FGFR inhibitor approved in Germany, erdafitinib, as well as to develop and test a second, independent activation model to allow robust predictions of the activation and drug response impact to enable a planned clinical trial to test FGFRi treatment for tumors with FGFR point mutations.

2:10 PM → 2:20 PM Platform Intro: Lighthouse Core Facility

2:20 PM → 3:00 PM Coffee Break

3:00 PM → 4:00 PM Keynote Lecture by Jens Puschhof

4:00 PM → 4:15 PM Overcoming Sotorasib-resistance in KRASG12C-mutated patient-derived pancreatic cancer organoids

Pancreatic ductal adenocarcinoma (PDAC) is a devastating cancer driven primarily by KRAS mutations. The KRASG12C mutation, while rare in PDAC, represents a targetable alteration with the inhibitors Sotorasib and Adagrasib approved for treatment of lung cancer. Early clinical trials show that while monotherapy with these inhibitors can provide initial clinical benefit in PDAC patients, all patients will eventually develop
progressive disease due to resistance mechanisms which are mostly unknown.To investigate these resistance mechanisms and to identify treatments to overcome resistance, we are inducing Sotorasib resistance in PDAC patient-derived organoids (PDOs) harboring the KRASG12C mutation. We aim to compare parental and resistant organoids to identify the transcriptional signatures driving resistance. This analysis will
include evaluating their differential responses to Sotorasib, Adagrasib, and and other emerging G12C inhibitors, as well as exploring strategic drug combinations that might overcome resistance. Initial characterization of the parental PDOs confirmed their sensitivity to both Sotorasib and Adagrasib, while KRASG12D-mutated and
KRASWT PDAC PDOs were resistant, demonstrating the mutation-specificity of these inhibitors. In addition, a drug combination screen in Sotorasib-sensitive, G12C-mutated PDOs identified combined KRASG12C and pan-ERBB inhibition via Afatinib as a promising, synergistic combination that could potentially delay or overcome resistance in this setting. Through molecular characterization and drug response profiling of
Sotorasib-resistant PDOs, we aim to identify additional therapeutic strategies for KRASG12C-mutated PDAC patients who develop resistance to targeted therapy.

4:15 PM → 4:30 PM Organoid-based response-prediction for targeted RAS+SHP2 and MEK/ERK+SHP2 inhibition in pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) remains a leading cause of cancer-related mortality, underscoring the urgent need for novel effective therapeutic strategies. Although direct interference with mutant RAS signaling, the omnipresent oncogenic driver in PDAC, is currently revolutionizing targeted cancer therapy, resistance to RAS inhibitors emerges rapidly necessitating rational combination approaches. Furthermore, with a growing array of RAS inhibitor classes entering clinical development, predictive biomarkers to guide individualized treatment selection remain largely undefined.

To address this, we have established a continuously expanding biobank of to date >100 primary patient-derived organoid (PDO) cultures from both pretreated and treatment-naïve PDAC tumors. More than 40% of these models are viable after freeze–thaw cycles and amenable to comprehensive molecular and pharmacologic interrogation. Leveraging this resource, we are systematically assessing the differential efficacy of mutant-specific and mutant-agnostic RASon and RASoff inhibitors, alongside MEK/ERK inhibitors, all in combination with SHP2 blockade - a central node in resistance development in response to MAPK pathway interference.

Pharmacologic screening via high-throughput viability assays is accompanied by microscopy and molecular analyses focusing on RTK-RAS-MAPK signaling dynamics. Transcriptomic and genomic profiling (RNASeq, WES) of treatment-naïve and resistant organoids - matched to their parental tumor tissue - elucidate mechanisms underlying intrinsic and acquired resistance and allow exploration of correlations with therapy response. To validate in vitro findings, representative sensitive and resistant PDOs are orthotopically xeno-transplanted into immunocompromised mice for randomized treatment trials with RAS±SHP2 inhibitors. In vivo tumor dynamics are monitored via MRI, followed by histological and molecular assessment post-treatment.

This integrative platform aims to identify predictive genetic and transcriptomic biomarker signatures for response to RAS+SHP2 and MEK/ERK+SHP2 combination therapies in PDAC, with the ultimate goal of informing rational design of future clinical trials and guiding personalized therapy approaches.

4:30 PM → 4:45 PM Patient-derived organoids (PDOs) as a companion tool to understand drug responses in the DKTK-funded SORATRAM IIT trial

Class-III BRAF mutations are increasingly identified across all tumor entities. They render the kinase inactive and - contrary to what one might expect – can lead to strong upregulation of the MAPK pathway through dimerization and strong allosteric activation of other Raf kinases such as RAF1 (c-RAF). Due to the inactivity of the kinase, selective BRAF inhibitors such as Vemurafenib or Dabrafenib are ineffective. Hence, the pan-Raf inhibitor Sorafenib comes into play. To enhance its inhibitory effect on the MAPK pathway and to counteract paradoxical activation at low concentrations, Sorafenib is combined with the MEK inhibitor Trametinib. The DKTK-funded IIT SORATRAM is a basket trial investigating the efficacy of Sorafenib and Trametinib in cancer with kinase inactive BRAF mutations. For this study, biopsies from patients that were eligible for enrollment in the SORATRAM clinical trial were processed and patient-derived-organoids (PDOs) from their various tumor entities were established. Several SORATRAM drug tests were carried out to determine the responsiveness of the patients in-vitro. Through Western Blots and RNA-sequencing of PDOs, we gained a deeper insight into the mechanisms of the SORATRAM combination for each patient individually. Importantly, we could show that it is possible to confirm drug responses in PDOs while the patient is still receiving guideline therapies. We expect that this approach will guide therapeutic decisions in individual patients and will be invaluable to interpret the clinical data of SORATRAM.

4:45 PM → 4:55 PM Platform Intro: FREEZE Biobank

4:55 PM → 5:30 PM What is needed to establish Pollar 1 and Pillar 2 in DKTK newtwork Freiburg?

Speaker: Melanie Börries (Institute of Medical Bioinformatics and Systems Medicine, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany 5 Faculty of Biology, University of Freiburg, Freiburg, Germany)

5:30 PM → 6:30 PM Poster Session

6:30 PM → 8:00 PM Dinner

Tuesday, July 8

9:00 AM → 10:00 AM Welcome Coffee

10:00 AM → 10:30 AM Michael Quante: Prevention and Early Detection of Esophageal Adenocarcinoma with Fluorescence Molecular Endoscopy

Invited Speaker

10:30 AM → 10:45 AM Decoding the spatial architecture of integrated electrophysiological and transcriptomic diversity in malignant brain tumors

Glioma cells form synaptic connections with neurons, facilitating tumor progression and therapeutic resistance, yet the microenvironmental drivers of this synaptogenesis remain unclear. To investigate the mechanisms regulating neuron-glioma connectivity, we developed ElectroGenomics, an integrative spatial electrophysiology and transcriptomics approach combining high-density multielectrode array (HD-MEA) recordings, spatial transcriptomics, retrograde tracing, and graph-based network analysis. Applying this framework across human cortical slice cultures and murine glioma models, we found that tumor infiltration induces localized peritumoral hyperexcitability alongside inflammatory activation of microglia. In particular, inflammatory SPP1+/TREM2+ microglia, resembling damage-associated states observed in stroke and trauma, were found to drive BDNF-mediated synaptogenesis and facilitate neuron-tumor network formation through close spatial interactions with NPC/OPC-like tumor cells and sprouting neurons. Using optogenetic stimulation of cortical neurons in a patient-derived xenograft model, we confirmed that increased neuronal activity promotes the recruitment and activation of SPP1+ microglia specifically within the tumor-infiltrative regions. Pathway analysis further identified STAT3 signaling as a central driver of this inflammatory microglial phenotype. Pharmacological inhibition of STAT3 signaling or depletion of microglia significantly disrupted neuron-glioma connectivity and reduced neural circuit integration in human neocortical slice models. Complementary functional calcium imaging demonstrated that STAT3 inhibition led to decreased intratumoral signaling and diminished neuron-glioma synapse formation. Together, our study identifies inflammatory SPP1+/TREM2+ microglia as key regulators of neuron-glioma synapse formation and highlights the STAT3 pathway as a promising therapeutic target to disrupt glioma integration into brain circuitry.

10:45 AM → 11:00 AM Non-invasive genotyping and MRD monitoring by circulating tumor DNA in patients with solid tumors patients receiving targeted treatment within molecular tumor boards

Introduction: Molecular tumor boards (MTB) stratify personalized targeted treatment for patients with rare and advanced cancers. Treatment response is assessed by CT/MRI, though limited by suboptimal sensitivity and specificity. Circulating tumor DNA (ctDNA) from blood plasma has emerged as a promising biomarker for noninvasive profiling of tumor mutational landscapes and disease monitoring. This study applied an ultra-sensitive next-generation sequencing (NGS) technology to evaluate ctDNA for tumor genotyping, early response prediction, and characterization of clonal heterogeneity in patients receiving targeted therapies within MTBs.
Methods: A custom-targeted NGS panel (ExTARGET) covering 266 genes across 540 kb, was applied to 167 plasma samples from 60 patients at distinct disease milestones. 24 healthy plasma samples were used to assess specificity. Digital droplet PCR (ddPCR) was used to assess concordance with NGS.
Results: In a pilot cohort of 21 patients, mutations were detected in 100% of pretreatment samples (median: 12 mutations/patient, range: 1-25). Target mutations guiding treatment initiation within MTBs, were identified in 80.9% (17/21 patients). Frequently mutated genes were BRAF (76%), KRAS (47%), ROS1 (61%) and TP53 (42%). NGS and ddPCR allele frequencies showed significant correlation ($R^2$=0.62, p<0.0001). Longitudinal tracking during therapy revealed that early ctDNA increases (4/4 cases) predicted disease progression at later timepoints. ctDNA dynamics reflected tumor burden and predicted progression in select patients.
Conclusion: We developed and implemented a NGS-based ctDNA profiling pipeline for patients with solid tumors within MTBs. Plasma genotyping identified targetable mutations in most cases. Monitoring ctDNA mirrors tumor burden and may enable early prediction of disease progression.

11:00 AM → 11:15 AM In Situ Peptide Identification by Parallel-Accumulation-Serial Fragmentation Supported MALDI MS/MS imaging: A Tool for Spatial Proteomics in Complex Disease Tissues

Spatial proteomics by matrix-assisted laser desorption/ionization (MALDI) imaging enables rapid, label-free peptide analysis directly from tissue sections. However, in situ peptide identification remains a major challenge, limiting the broader utility of this technique. In this study, we present a novel workflow that integrates Trapped Ion Mobility Spectrometry-based Parallel Accumulation–Serial Fragmentation into MALDI imaging to enable multiplexed MS/MS imaging and MASCOT peptide-to-spectrum matching for spatial peptide identification. We demonstrate the feasibility of this pipeline across three distinct samples: a tumor xenograft model, mouse kidney tissue, and an amyloidosis tissue microarray (TMA) comprising different subtypes. In each case, iprm-PASEF enabled the identification of multiple tryptic peptides in a single imaging experiment, with spatially resolved fragment ion maps and identifications corroborated by LC-MS/MS and fragment colocalization. In the TMA, we successfully identified seven amyloidosis-associated peptides, including markers from vitronectin, apolipoprotein E, and transthyretin receptor, with clear spatial correlation to Congo red-positive deposits. These three tissue types, xenograft, kidney, and amyloidosis TMA, collectively illustrate the method’s applicability to resolve peptide distributions and molecular characterization from complex physiological and pathological heterogeneous tissues. These findings underscore the promise of tryptic peptide MS/MS MALDI imaging for advancing spatial proteomics in oncology and pathology research, with potential applications in tumor characterization, microenvironment profiling, and treatment response studies, particularly when integrated with complementary omics and histological approaches, though further validation across different tissue samples is needed.

11:15 AM → 11:30 AM Preclinical Evaluation of MT1-MMP-Targeting Bicyclic Peptides for Radiotheranostic Applications

Membrane type 1 matrix metalloproteinase (MT1-MMP) is crucial in extracellular matrix degradation, which facilitates cancer progression and metastasis. Previous studies have shown the feasibility of using phage display-derived radiolabelled bicyclic peptides for positron emission tomography (PET) imaging. This study aimed to identify and characterize novel MT1-MMP-binding bicyclic peptides with an improved pharmacokinetic profile.

Four novel MT1-MMP-targeting bicyclic peptides (BCY1, BCY2, BCY3, and BCY4) were radiolabelled with either gallium-68 or lutetium-177. We assessed various physicochemical properties, including binding affinity, serum stability, and logD values. Cell binding and internalization were evaluated using MT1-MMP-expressing HT1080 cells. In vivo performance was analyzed in MT1-MMP+ tumor-bearing nude mice via µPET/MR imaging up to 2 hours post-injection (p.i.), followed by an organ distribution analysis (n = 3 for each peptide).
Results
All peptides exhibited nanomolar binding affinity (4.1 - 9.8 nM), with radiochemical purity exceeding 99 %. They demonstrated high serum stability, and their logD values ranged from - 3.6 to - 2.6. In vitro studies confirmed high specificity and minimal off-target binding (1 - 4 %). High tumour-to-background contrast was achieved within 30 minutes p.i. for BCY1, BCY2, and BCY4. Organ distribution studies revealed significant tumor uptake (12 - 25 % injected dose per gram, %ID/g) of all bicyclic peptides at 1-hour p.i., with BCY1 and BCY4 exhibiting the lowest off-target binding, aside from kidneys (5.8 %ID/g and 6.1 %ID/g, respectively).
Conclusion
BCY1 and BCY4 demonstrated optimal pharmacokinetic profiles characterized by high tumor uptake, specificity, and rapid blood clearance. Further translational research is essential to evaluate their full potential for radiotheranostic applications.

11:30 AM → 12:00 PM Evelyn Ullrich: From llama towards immunotherapy –A VHH binding domain enhances CLEC12A-CAR-NK cell therapy for treatment of AML

Invited Speaker

12:00 PM → 1:00 PM Lunch

1:00 PM → 1:15 PM Extracorporeal Photopheresis resolves immune checkpoint inhibitor associated colitis through local adiponectin induction

The development of immune-related adverse events (irAEs) in cancer patients receiving immune checkpoint inhibitors (ICIs) cause morbidity, necessitates treatment cessation and limits ICI efficacy. Comparing different first- and second-line irAE treatments, we found that glucocorticosteroids, TNFα blockade, and α4β7-integrin inhibition reduced anti-tumor immunity in mice. We compared these therapies against extracorporeal photopheresis (ECP) and found that ECP has no negative effect on anti-tumor immunity in multiple preclinical tumor models. Based on these findings, we tested ECP in different ICI-colitis models and observed significantly reduced colitis severity after treatment. Mechanistically, we identified that ECP-treated splenocytes accumulate specifically in the inflamed intestinal tract, but not the tumor microenvironment. Apoptotic splenocytes were engulfed by intestinal phagocytes, which rendered these towards an anti-inflammatory phenotype. Immunosuppressive macrophages secreted adiponectin to resolve inflammation in the intestinal tract. Local adiponectin production elicited a tissue-specific effect by reducing pro-inflammatory tissue-resident memory T-cell activation, CD4+IFN-ү+ T-cells and inflammatory myeloid cells, while sparing tumor-specific T-cell development.
Following our preclinical investigations, we tested ECP in a prospective phase-Ib/II trial (EudraCT-No.2021-002073-26) with 30 patients and found low ECP-related toxicity. At week 12 of therapy, the overall response rate (ORR) for all irAEs was 96%; the ORR for colitis was 100%. The colitis-specific complete remission rate was 93%. Glucocorticosteroids could be reduced for all patients after ECP-therapy. The ECP-adiponectin axis reduced intestinal activation in patients with ICI-colitis without evidence of loss of anti-tumor immunity.
In conclusion, we identified ECP-induced adiponectin as an immunomodulatory mechanism to control ICI-induced inflammation without blocking anti-tumor immunity.

1:15 PM → 1:30 PM Base Editing Unlocks NK Cell Potential for Cancer Immunotherapy

Natural killer (NK) cells are critical components of the innate immune system, capable of targeting tumor and virus-infected cells. Their function is regulated by a balance of activating and inhibitory receptors. Among these, NKG2A—encoded by the KLRC1 gene—recognizes the non-classical MHC molecule HLA-E on target cells, delivering inhibitory signals that suppress NK cell cytotoxicity and contribute to immune evasion by tumors. CRISPR/Cas9-mediated disruption of KLRC1 has been explored to enhance NK cell function, but its clinical application is constrained by suboptimal efficiency and risks associated with DNA double-strand breaks (DSBs), including genotoxicity. In this study, we employed adenine base editing (ABE) to achieve precise and safe KLRC1 knockout in primary human NK cells. A panel of guide RNAs (gRNAs) was tested, and one highly effective gRNA/ABE combination was selected for direct comparison with CRISPR/Cas9. ABE editing achieved >95% knockout efficiency at both genomic and protein levels without being dependent on DSBs. In contrast, Cas9 editing with the same gRNA yielded lower efficiency and detectable off-target activity. In contrast, evaluation of specificity using UCAST-Seq confirmed minimal off-target effects in ABE-edited NK cells. Functional assays confirmed complete loss of NKG2A expression and significantly enhanced cytotoxicity against HLA-E–positive tumor cells. These results highlight ABE as a highly efficient and precise platform for KLRC1 knockout in NK cells, offering a safe alternative to conventional gene editing for the development of next-generation NK cell–based immunotherapies.

1:30 PM → 1:45 PM CD73 and MEK Inhibition improve T Cell function in NRAS-Mutant AML: A Strategy for Post-Transplant Immune Surveillance

Relapse after allogeneic hematopoietic stem cell transplantation (allo-HCT) remains a major obstacle in the treatment of acute myeloid leukemia (AML), often driven by immune escape mechanisms. NRAS mutations, found in ~12% of AML cases, activate RAS-MAPK signaling and are frequently acquired late in disease progression, suggesting a role in immune evasion and post-transplant relapse.
Using a syngeneic transplantation mouse model with NRASG12D -transduced hematopoietic stem cells (HSCs), we show that NRAS activation upregulates CD73 on myeloid cells and suppresses T cell function—marked by reduced TNF-α, impaired CD4⁺/CD8⁺ proliferation, and increased Tregs. These immunosuppressive effects were largely reversed upon transplantation of CD73-deficient, NRAS-transduced cells, which also exhibited increased MHC class II expression
In an allogeneic model, NRAS-driven leukemia induced similar T cell dysfunction, including reduced effector proliferation and cytokine production. CD73 inhibition restored T cell effector function, increased granzyme B, enhanced memory differentiation, and further upregulated MHC-II.
MEK inhibition (Trametinib) reduced CD73 expression, enhanced T cell proliferation, and improved leukemia control in a recall immunity experiment, suggesting durable anti-leukemic memory.
Our findings identify CD73 as a central immune checkpoint in NRAS-mutant AML. Targeting CD73 and MEK represents a promising strategy to enhance post-transplant immune surveillance and prevent relapse

1:45 PM → 2:15 PM Coffee Break

2:15 PM → 2:30 PM From functional imgaging to new traetment approaches in radaition oncology

Tumor hypoxia and high cell density are a well-documented phenomenon in tumours and are key factors contributing to radioresistance. Consequently, overcoming these factors are a major challenge in modern radiation oncology.

Functional imaging using F-MISO-, FDG-PET-CT and multiparametric MRT provide non-invasive methods for detecting and quantifying tumor hypoxia and cellularity at a macroscopic level.
In a prospective, exploratory analysis conducted by us, we were able to determine the spatial distribution, intensity and progression of tumour hypoxia and cell density using sequential imaging in cancers of head and neck

In cooperation with the Karolinska Institutet we developed a model for calculating expected tumor control probability (TCP). This model forms the basis for the creation of individualized radiation plans that achieve TCPs of (theoretically) 80%/90%/95% considering the biological and visible properties of the tumour cells The planned (intratumoral) dose escalation should be delivered as precisely as possible (in terms of spatial localization regarding hypoxia dynamics) and ideally as effective as possible in restoring normoxia. For this reason, dose escalation in our project is planned as an initial “boost” at the beginning of radiochemotherapy as proposed from validated simulation models.

We are presenting the outlines of the Phase-I HIBERNATE-trial (Hypoxia and cell density imaging based boost for enhanced radiation therapy in head and neck affecting tumors)
In this trial we individualize radiation treatment based on biological properties visible through functional imaging comparable to molecular precision oncology. This is a fundamental change in radio oncological treatment approaches and will therefore have visionary character.

2:30 PM → 2:45 PM Characterisation of a Fluorescent Dye Library using a Dual-Labelled PSMA-617-based Tracer

Introduction: In the field of dual-labelled tracers and fluorescence-guided surgery (FGS), ICG and IRDye800CW have been established as the most commonly used dyes. However, fluorescent dyes have continued to evolve. In order to investigate the suitability of such new dyes for potential clinical application, a library of dyes was conjugated to a PSMA-617-based tracer (DP). The aim was to identify a candidate with the most promising pharmacokinetic and optical properties to improve precise real-time feedback during surgery. Materials and Methods: Pharmacokinetic behaviour was assessed in BALB/c nu/nu mice bearing LNCaPPSMA+ xenografts by μPET/MRI at 1h and 2h after injection of 0.5 nmol (2.8 kDa - 3.2 kDa) of the 68Ga-labelled hybrid molecules. Fluorescence was determined ex vivo as well as organ distribution 2 h p.i.. Results: In vivo studies revealed different pharmacokinetic profiles depending on the conjugated dye. Two candidates showed rapid clearance 1 h p.i. with high tumour uptake 2 h p.i.: DP-09 (9.14 %ID/g tumour, 26.27 %ID/g kidney) and DP-15 (7.67 %ID/g tumour, 7.68 %ID/g kidney). In contrast, DP-24 showed a slower clearance at 1 h p.i., but three times higher tumour accumulation compared to the others (22.94 %ID/g tumour, 61.97 %ID/g kidney). Conclusion: The three candidates identified were shown to have a promising pharmacokinetic profile after conjugation with the fluorescent dyes, making them suitable for further investigation. With improved photostability and higher quantum yields compared to ICG and IRDye800CW, the selected candidates may lead to an advantage in FGS.

2:45 PM → 2:55 PM Platform Intro: FREpi : a curated epigenetic inhibitor screening library for target discovery and validation

2:55 PM → 3:15 PM Wrap Up by Melanie Börries and Robert Zeiser

3:15 PM → 4:15 PM Young Investigator Get Together