The goal of the Clinical Translation Group “T-cell fitness” is to bring innovative T-cell technologies into clinical application. Our primary focus is to develop and manufacture genetically enhanced T-cell therapies that improve antitumor immunity through genetic enhancement of T-cell functionality and survival and translate these advances into early-phase clinical trials. By integrating cutting-edge T-cell engineering with rigorous preclinical and GMP-compliant manufacturing processes, we aim to provide next-generation T-cell therapies for patients with solid tumors.

Advancing Towards Clinical Application

Following preclinical validation, we transition to pre-GMP and GMP manufacturing, ensuring high-quality production through rigorous quality control assays. These include assessments of identity, purity, sterility, and stability, preparing the cell product for clinical application. A critical component of our strategy is the use of stem-like T-cell platforms to enhance long-term persistence, while integrating safety switches to improve the safety profile of the therapy. One of our leading programs, ESOSTEM155, is a NY-ESO-1 TCR-modified stem-like T-cell therapy engineered to enhance antitumor function through miR-155 modulation.

ESOSTEM155 (NY-ESO-1 TCR-modified stem-like T cells overexpressing miR-155 SNP rs377265631). Manufacturing and Quality control

First-in-Human Clinical Trial

We are currently preparing a Phase I clinical trial for patients with solid tumors, which will be conducted at the Early Clinical Trial Unit at the University Hospital Regensburg: ESOSTEM155. A phase I safety, dose-finding, and feasibility trial of NY-ESO-1 TCR-modified stem-like T cells overexpressing miR-155 SNP rs377265631 in patients with metastatic synovial sarcoma and myxoid or round cell liposarcoma.

From Discovery to Clinical Translation: Unlocking the Therapeutic Potential of T Cells

To continuously improve our cell therapies, we investigate novel molecular strategies that can further enhance T-cell fitness and persistence. One approach involves identifying hidden genetic regulators within T cells that can be synthetically modulated to enhance their therapeutic efficacy. A key example is the activation of LMO4 in T cells, which reveals its previously untapped potential for boosting antitumor responses.

Once identified, these novel T-cell modifications undergo functional validation in preclinical models, using both CAR and TCR constructs in syngeneic and xenograft solid tumor settings. By systematically comparing different approaches, we aim to select the most promising candidates for clinical development.

Tumor size and survival curve of gp100-melanoma-bearing wild-type mice following the transfer of either control cells (gray) or Lmo4-overexpressing gp-100 targeting CD8+ T cells (blue), in combination with a gp100 vaccine and IL-2. Red represents the untreated group.

Bridging Research and Clinical Application

By closely integrating basic research, preclinical validation, GMP manufacturing, and early clinical testing, our goal is to seamlessly translate groundbreaking T-cell therapies into clinical practice, ultimately improving outcomes for patients with hard-to-treat solid tumors.

Visit the complete publications list on Google Scholar:

https://scholar.google.com/citations?user=yccc2TYAAAAJ&hl=de&oi=ao

Here is a selection of the most important publications from the last few years:

Schelker RC, Fioravanti J, Mastrogiovanni F, Baldwin JG, Rana N, Li P, Chen P, Vadász T, Spolski R, Heuser-Loy C, Slavkovic-Lukic D, Noronha P, Damiano G, Raccosta L, Maggioni D, Pullugula S, Lin JX, Oh J, Grandinetti P, Lecce M, Hesse L, Kocks E, Martín-Santos A, Gebhard C, Telford WG, Ji Y, Restifo NP, Russo V, Rehli M, Herr W, Leonard WJ, Gattinoni L. LIM-domain-only 4 (LMO4) enhances CD8+ T-cell stemness and tumor rejection by boosting IL-21-STAT3 signaling. Signal Transduct Target Ther. 2024 Aug 9;9(1):199. doi: 10.1038/s41392-024-01915-z. PMID: 39117617; PMCID: PMC11310520.

Baldwin JG, Heuser-Loy C, Saha T, Schelker RC, Slavkovic-Lukic D, Strieder N, Hernandez-Lopez I, Rana N, Barden M, Mastrogiovanni F, Martín-Santos A, Raimondi A, Brohawn P, Higgs BW, Gebhard C, Kapoor V, Telford WG, Gautam S, Xydia M, Beckhove P, Frischholz S, Schober K, Kontarakis Z, Corn JE, Iannacone M, Inverso D, Rehli M, Fioravanti J, Sengupta S, Gattinoni L. Intercellular nanotube-mediated mitochondrial transfer enhances T cell metabolic fitness and antitumor efficacy. Cell. 2024 Nov 14;187(23):6614-6630.e21. doi: 10.1016/j.cell.2024.08.029. Epub 2024 Sep 13. PMID: 39276774; PMCID: PMC11623344.

Schelker RC, Gattinoni L. Releasing the brake: CTLA-4 loss turbocharges CAR T cells. Immunity. 2023 Oct 10;56(10):2180-2182. doi: 10.1016/j.immuni.2023.09.006. PMID: 37820579. ‪‬‬‬‬‬‬

2025-2027

Berlin Institute of Health at Charité’s national translational projects in gene and cell therapy (GCT) program ESOSTEM155 (NY-ESO-1 TCR-modified stem-like T cells overexpressing miR-155) preclinical development

2025-2026

G-Rex® Grant Program Process development and optimization of a G-Rex® centric manufacturing process to produce CAR-T cells with T stem cell memory (TSCM) phenotype

2022-2023

Regensburger Forschungsförderung in der Medizin (ReForM) B, Faculty for Medicine, University Hospital Regensburg The role of the transcriptional regulator Lmo4 in CD8+ T cell stemness, memory formation and antitumor immunity

2021-2022

Gerok Position Deutsche Forschungsgemeinschaft (DFG) within Sonderforschungsbereich (SFB) Transregio 221 The role of the transcriptional regulator Lmo4 in CD8+ T cell stemness, memory formation and antitumor immunity

2019-2021

DFG Auslandsstipendium The role of the transcriptional regulator Lmo4 in CD8+ T cell stemness, memory formation and antitumor immunity

2012-2014

Regensburger Forschungsförderung in der Medizin (ReForM) A, Faculty for Medicine, University Hospital Regensburg The importance of mesenchymal stem cells (MSCs) for the genesis of leukemia

Dr. Dr. Roland Schelker

Head of Translation Group | T-Cell Fitness

Tel: +49 941 944-18374
Email: Roland.Schelker@ukr.de

Dr. Dr. Roland Schelker

Head of Translation Group | T-Cell Fitness

Pallavi Kadam

Postdoctoral Scientist

Gaurang Telang

Research Technician

Franziska Roscher

PhD Student

Lab Life

There is life outside the laboratory: The Leibniz Institute places great value on our scientists developing the team spirit both in and out of work. Here are the photos to prove it!