Hematology and Immune Engineering

Rewiring the immune system to make cancer controllable.

The challenge
Blood cancers such as leukemia and multiple myeloma evolve to evade the immune system, leaving even the best immunotherapies ineffective for many patients. Relapse remains the biggest obstacle in modern hematology.

Our vision
We are engineering immune resilience: building T cells that recognize hidden tumor antigens (Kehl et al., JITC 2022), resist suppression (Friedrich et al., Cancer Cell 2023), and persist long enough to prevent relapse (Kilian*, Friedrich*, Lu* et al., Sci Immunol​ 2024). Using single-cell profiling and advanced TCR discovery, we recently uncovered conserved tumor targets across otherwise distinct blood cancers, laying the foundation for truly universal immunotherapies (Wagner*, Kehl*, Steiger*, Boschert* et al., BioRxiv 2025). Our goal is bold yet simple: to make cancer a disease that the immune system can permanently control.

Keeping the immune system young to extend healthy life.

The challenge
Aging erodes the immune system, making us more vulnerable to infections, cancer, and poor vaccine responses. The thymus - the organ that generates T cells - gradually shuts down, leaving our defenses depleted.

Our vision
We are pioneering in vivo immune rejuvenation: mRNA-based strategies that transiently restore thymic function, expand T cell diversity, and revitalize immunity in aging organisms. With next-generation spatial profiling methods (Liu*, Friedrich*, Raichur* et al., BioRxiv 2025) and delivery systems (Kreitz, Friedrich et al., Nature 2024), we aim to target and reprogramm specific cells and organs with precision. Our aim is to not only treat age-related immune decline but to extend healthy lifespan by keeping the immune system young, adaptive, and resilient.

Harnessing artificial intelligence to predict human immune responses and design safer gene therapies.

The challenge
No two patients respond the same way to treatment. The complexity of the human immune system makes it hard to predict who will benefit - and risky to introduce transformative tools like mRNA therapeutics or CRISPR gene therapies without knowing how the immune system will react.

Our vision
We harness artificial intelligence to decode and predict human immune responses. By integrating clinical, genomic, and immunological data, we are building decision-support tools that help oncologists choose the right therapy for each patient. We recently leveraged AI-guided protein design reduces the immunogenicity of genome-editing tools, paving the way for safe, patient-tailored gene therapies (Raghavan*, Friedrich* et al., Nat Commun​ 2025). Our vision is true precision medicine: immunotherapies and gene therapies designed not just for diseases, but for individuals.

Turning discoveries into treatments without waiting decades.

The challenge
Great ideas in the lab often never reach patients - lost to regulatory hurdles, manufacturing complexity, or decades of delay.

Our vision
Directly out of our lab, we accelerate translation by leading experimental first-in-human trials that move synthetic immunology from concept to clinic. Our PERSIST-B7H6 trial is the first to test CRISPR-edited CAR-T cells engineered for enhanced persistence in Germany. Building on our preclinical discoveries in immune rejuvenation, we are now advancing mRNA-driven immune reprogramming toward human testing. Our lab is part of the German Cancer Consortium (DKTK) and all of our clinician scientists treat patients at the Department of Hematology, Oncology and Rheumatology at Heidelberg University Hospital. By bridging discovery with patient care at our clinical department, we shorten the path from bench to bedside and ensure that innovation does not wait decades, but reaches our patients as soon as possible.