Maximilian Koch

All Publications

• COMPLETE ENDOGENOUS TCR ABLATION IS REQUIRED TO ELIMINATE CD3 COMPETITION AND MISPAIRING IN TCR GENE THERAPY Koch, M., Kahveci, H., Ponce, L., Heitzeneder, S. SAGE PUBLICATIONS INC. 2026: 18S

  View details for Web of Science ID 001814021400033

• Longitudinal single-cell atlas of GD2-CAR T cell therapy in H3K27M-mutant diffuse midline glioma identifies humoral and cellular anti-CAR immunity Chen, Y., Song, K., Desai, M. H., Huang, Y., Iswari, N., Ehlinger, Z. J., Daghagh, H., Koch, M. R., Reynolds, K., Mo, K. C., Tsui, K. C., Rietberg, S., Hamilton, M. P., Prabhu, S., Partap, S., Mahdi, J., Egeler, E., Feldman, S. A., Heitzeneder, S., Yamada-Hunter, S. A., Sotillo, E., Sahaf, B., Good, Z., Monje, M., Ramakrishna, S., Mackall, C. L. AMER ASSOC CANCER RESEARCH. 2026

  View details for DOI 10.1158/1538-7445.AM2026-6463

  View details for Web of Science ID 001734512300036

• EPICYCLE: A confirmatory preclinical study of the anti-rhabdomyosarcoma efficacy of BET bromodomain and cyclin-dependent kinase 9 inhibitors. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie Haller, B., Richter, G. H., Wachtel, M., Schuler, L., Regina, C., Renz, B., Jens, M., Bechtold, I., Gadasheva, Y., Hamed, E., Kisele, S., Knoblauch, M., Koch, M. R., Lupar, D., Nakano, S., Pardon, K., Pärschke, P. J., Winter, C., Tölch, U., Schäfer, B. W., Banito, A., von Lüttichau, I., Hettmer, S. 2025; 192: 118704

  Abstract

  Hypothesis-driven academic research identifies interventions with likely disease-specific effects. Yet, many candidate drugs fail upon further development, emphasizing the need for acquisition of more robust preclinical data. We demonstrate that planning and executing multicentre confirmatory preclinical studies in an academic setting by applying the quality standards of early phase clinical trials is feasible. Randomization, blinding, stratification by sex of and quality control measures were carried out successfully. The primary objective of our specific study - to confirm synergistic effects of BET bromodomain protein 4 (BRD4) and cyclin-dependent kinase 9 (CDK9) inhibitors against PAX3::FOXO1 (P3F)-positive rhabdomyosarcoma (RMS) - was not met. Post-hoc analyses support that single-agent BRD4 inhibition by JQ1 effectively reduced the growth and viability of P3F+ RMS cells ex vivo with adequate on-target activity as evidenced by reduced expression of P3F, MYCN, MYOG, and MYOD. The antiproliferative effects of JQ1 and vincristine were comparable, and there was trend towards reduced and delayed xenograft growth in JQ1-treated mice. Yet, in vivo assays were flawed by lower xenograft penetrance, variable xenograft latency, gastrointestinal toxicity, and inadequate on-target activity of drugs. We conclude that confirmatory preclinical trials allow for robust assessment of the efficacy of candidate interventions and reduce bias in academic research. The study platform established here provides a framework that may be of particular benefit for the development of new drugs for rare cancers.

  View details for DOI 10.1016/j.biopha.2025.118704

  View details for PubMedID 41161003

• CagA-dependent Hobit+ gastric tissue-resident memory T cells confer full protection from Helicobacter pylori reinfection. Gut Gong, R., Huang, B., Ralser, A., Friedrich, V., Mibus, C., Engelsberger, V., Koch, M. R., Skerhut, M., Giese, T., Andrä, I., Vieth, M., van Gisbergen, K. P., Semper, R. P., Gerhard, M., Mejías-Luque, R. 2025

  Abstract

  Helicobacter pylori infection is the most prevalent bacterial infection worldwide. Attempts to develop a vaccine have not been successful, partly due to the absence of well-defined immune correlates of protection. The inflammatory response to H. pylori infection is characterised by the recruitment of T cells expressing markers of tissue-resident memory T (TRM) cells to the gastric mucosa. However, the function of TRM cells in gastric tissue during H. pylori reinfection remained poorly understood.We aimed to investigate the induction, development and function of gastric TRM cells during primary and secondary H. pylori infection.We characterised gastric H. pylori-specific TRM cells in mice and humans by flow cytometry, immunohistochemistry, immunofluorescence, ChipCytometry staining and single-cell RNA sequencing. The function of gastric TRM cells was established in H. pylori eradication and reinfection experiments as well as by targeted depletion of Hobit+ TRM cells and neutrophils in mice.Expression of the transcription factor Hobit governs the induction and development of gastric TRM cells, which largely depend on the presence of the H. pylori virulence factor Cytotoxin-associated gene A. H. pylori-specific CD4+ and CD8+ TRM cells resided long-term in the stomach and conferred complete protection from reinfection with the help of neutrophils. Gastric CD8+ TRM cells exhibited varying Hobit expression levels and clustered into distinct subgroups based on distinct transcriptomic and cytokine profiles, suggesting functional specialisation.These findings establish gastric TRM cells as bona fide correlates of protection against H. pylori, highlighting their potential for future prophylactic and therapeutic strategies.

  View details for DOI 10.1136/gutjnl-2025-334781

  View details for PubMedID 40473399

• CagA-specific Gastric CD8+ Tissue-Resident T Cells Control Helicobacter pylori During the Early Infection Phase. Gastroenterology Koch, M. R., Gong, R., Friedrich, V., Engelsberger, V., Kretschmer, L., Wanisch, A., Jarosch, S., Ralser, A., Lugen, B., Quante, M., Vieth, M., Vasapolli, R., Schulz, C., Buchholz, V. R., Busch, D. H., Mejías-Luque, R., Gerhard, M. 2023; 164 (4): 550-566

  Abstract

  Infection with Helicobacter pylori strongly affects global health by causing chronic gastritis, ulcer disease, and gastric cancer. Although extensive research into the strong immune response against this persistently colonizing bacterium exists, the specific role of CD8+ T cells remains elusive.We comprehensively characterize gastric H pylori-specific CD8+ T-cell responses in mice and humans by flow cytometry, RNA-sequencing, immunohistochemistry, and ChipCytometry, applying functional analyses including T-cell depletion, H pylori eradication, and ex vivo restimulation.We define CD8+ T-cell populations bearing a tissue-resident memory (TRM) phenotype, which infiltrate the gastric mucosa shortly after infection and mediate pathogen control by executing antigen-specific effector properties. These induced CD8+ tissue-resident memory T cells (TRM cells) show a skewed T-cell receptor beta chain usage and are mostly specific for cytotoxin-associated gene A, the distinctive oncoprotein injected by H pylori into host cells. As the infection progresses, we observe a loss of the TRM phenotype and replacement of CD8+ by CD4+ T cells, indicating a shift in the immune response during the chronic infection phase.Our results point toward a hitherto unknown role of CD8+ T-cell response in this bacterial infection, which may have important clinical implications for treatment and vaccination strategies against H pylori.

  View details for DOI 10.1053/j.gastro.2022.12.016

  View details for PubMedID 36587707