Max-Eder-Research for Molecular Immunetherapy (Müller)

Max-Eder Research Group for Molecular Immunetherapy

Lab Members

Fabian Müller, MD, Principle Investigator
Dr. rer. nat. Franziska Gsottberger, Post-Doc
Dr. rer. nat. Hao Yao, Post-Doc
Dr. med. Julia Katharina Scholz, Physician Scientist
Giulia Benintende, MD PhD graduate program, Physician Scientist
Dr. med. Isabel Korte, Clinician Scientist
Alessia Crocione, graduate student
Veronika Friedrich, graduate student
Lisa Mellenthin, V-MTLA
Srdjan Petkovic, MTLA

Research Focus

Cell therapy has become one of the most remarkable achievements of modern hematology and oncology. As a living drug, they deliver hope to patients with previously incurable diseases including cancer and autoimmune diseases and may soon also support treatment of infectious diseases and hereditary disorders.

However, cell therapy still faces many challenges such as harsh microenvironments that prevent optimal function. Furthermore, we lack biomarker to predict which patient needs more than just a 2^nd gen CAR, what co-treatment would be needed in a distinct microenvironment, or simply what cell dynamics and state of inflammation in a given patient could mean functionally for the expanding and invading CAR T cell in a patient and within a patient’s tumor microenvironment. Leveraging our experience in the field of B cell driven inflammatory auto-immune diseases, we approach these problems from various angles such as understanding lymphoma-driven inflammation and it’s many effects on cell therapy, how to modulate this inflammation in a targeted and disease specific manner, and use this novel understanding to enhance CAR T cell therapy in fully immune competent models of aggressive and indolent lymphoma in vivo. With the central lab theme of understanding resistance to immunotherapy through translational science, we aim to improve treatment and as such, outcomes for our patients in hem, rheum, gastroenterology, and other emerging entities.

Thematic Focus

innovativ approaches for antibody based cancer therapy
lymphoma induced immun-modulation and impact on CAR T cells
immunology of the tumor-micromilieu

Figure caption:

Central of our research is the understanding of the cross-talk of B cells and T cells and its effects on the tumor microenvironment, cell therapy, systemic inflammation and the sometimes lasting effects of the disease on the immune system of the patients. Based on Müller, F. Innere Medizin 66, 810–817 (2025). Doi 10.1007/s00108-025-01945-x

Collaborations

internal:

Prof. Dr. Metzler (Children´s Hospital, Head, Dept. of Pediatric Oncology)
Prof. Dr. Nitschke (Biology, Head, Division of Genetics)
Prof. Dr. Christian Pilarsky (Operative Surgery, Head, Laboratory of Functional Genomics)
Prof. Dr. Stürzl (Dept. of experimental Surgery, Head)

external:

Dr. Vidya Chandramohan, Associate Prof. in Neursosurgery, Duke University Medical Center
Dr. Ira Pastan, National Institutes of Health, Bethesda, MD, USA
Dr. Alan S. Wayne, Children's Hospital Los Angeles, CA, USA
Medimmune, LLC, Gaithersburg, MD, USA

Research Support (alphabetical order, only active):

Bayerisches Zentrum für Krebsforschung (BZKF)
Britsol Meyers Squibb (Research grant of the Action Network)
Deutsche Forschungsgemeinschaft (DFG)
Deutsche Krebshilfe e.V.
Interdisziplinäres Zentrum für Krebsforschung
STAEDTLER-Stiftung

Selected Publications

George R, Gsottberger F, Ammon A, Wendland K, Mellenthin L, Mackensen A, Müller F. Triton X-114 and Amine-Based Wash Strategy Reduces Lipopolysaccharides to FDA Limit and Achieves Purer, More Potent Recombinant Immunotoxin. Bioconjug Chem. 2021 Apr 21;32(4):713-720. doi: 10.1021/acs.bioconjchem.1c00013. Epub 2021 Apr 1. PubMed PMID: 33793193.

Müller F, Cunningham T, Stookey S, Tai CH, Burkett S, Jailwala P, Stetler Stevenson M, Cam MC, Wayne AS, Pastan I. 5-Azacytidine prevents relapse and produces long-term complete remissions in leukemia xenografts treated with Moxetumomab pasudotox. Proc Natl Acad Sci U S A. 2018 Feb 20;115(8):E1867-E1875. doi: 10.1073/pnas.1714512115. Epub 2018 Feb 5. PubMed PMID: 29432154.

Müller F, Stookey S, Cunningham T, Pastan I. Paclitaxel synergizes with exposure time adjusted CD22-targeting immunotoxins against B-cell malignancies. Oncotarget. 2017 May 9;8(19):30644-30655. doi: 10.18632/oncotarget.16141. PubMed PMID: 28423727; PubMed Central PMCID: PMC5458156.

Müller F, Cunningham T, Liu XF, Wayne AS, Pastan I. Wide Variability in the Time Required for Immunotoxins to Kill B Lineage Acute Lymphoblastic Leukemia Cells: Implications for Trial Design. Clin Cancer Res. 2016 Oct 1;22(19):4913-4922. Epub 2016 Apr 25. PubMed PMID: 27114443; PubMed Central PMCID: PMC5050065.

Liu X, Müller F, Wayne AS, Pastan I. Protein Kinase Inhibitor H89 Enhances the Activity of Pseudomonas Exotoxin A-Based Immunotoxins. Mol Cancer Ther. 2016 May;15(5):1053-62. doi: 10.1158/1535-7163.MCT-15-0828. Epub 2016 Mar 3. PubMed PMID: 26939705; PubMed Central PMCID: PMC4873377.

Hollevoet K, Mason-Osann E, Müller F, Pastan I. Methylation-associated partial down-regulation of mesothelin causes resistance to anti-mesothelin immunotoxins in a pancreatic cancer cell line. PLoS One. 2015 Mar 24;10(3):e0122462. doi: 10.1371/journal.pone.0122462. eCollection 2015. PubMed PMID: 25803818; PubMed Central PMCID: PMC4372481.