Triple-threat approach packs a punch against hard-to-hit tumours

Science has made great strides in treating cancer, yet many tumours eventually become resistant to therapy. The Image-guided and Functionally Instructed Tumor Therapies (iFIT) Cluster of Excellence at the University of Tübingen, Germany aims to change that.

Founded in 2019 with a grant from the German Research Foundation (DFG), iFIT is the only oncology cluster of excellence in the country. The group unites three key areas of cancer research: functional target discovery and molecular therapies, immunotherapy, and multiparametric imaging. By bringing these fields together under one institutional roof, the cluster aims to generate new insights on the biological processes within tumours, informing the development of therapies that target weak points and help keep resistance at bay.

“We realized we’re in a unique situation,” says Lars Zender, one of the three leaders of the cluster. It’s rare, he notes, that all three disciplines are pursued at such a high level in the same place, with a long track record of collaboration. “With teams working at the boundaries of these areas, you can really do holistic translational cancer research.”

Functionally instructed molecular therapy is Zender’s area of expertise. They use technologies such as RNAi and CRISPR to screen tumours for new therapeutic targets. The university’s strong medicinal and pharmaceutical chemistry departments mean their findings are being translated into new experimental treatments.

The second research area is immunotherapy, led by iFIT co-founder Hans-Georg Rammensee, who researches personalized peptide vaccines for cancer patients. The cluster also develops bispecific antibodies, which direct T cells to specific targets on malignant cells.

Bernd Pichler heads the third area, functional and multiparametric imaging, which combines imaging methodologies to unlock new molecular insights. Again, the university has a long track record — PET-MRI, for example, was developed at Tübingen (Judenhofer, M.S. et al. Nat Med 14, 459-465; 2008). The cluster now has its own pipeline for PET imaging tracers, targeted molecular labels that can reveal features such as metabolic activity within a tumour.

A bridge from cell biology to the clinic

The cluster aims to build infrastructure, including professorships and new independent research groups, to foster innovation at the interface between these three disciplines. It has attracted high-flying lab heads from around the world. Bettina Weigelin, a cell biologist specialising in microscopic imaging technologies, was among the first to join. “It was a unique opportunity,” she says. “I was able to build this infrastructure of microscopic imaging and integrate it with the macroscopic imaging.”

Weigelin is using her expertise in microscopic imaging of the behaviour of immune cells within tumours to create a bridge between fundamental cell biology and larger-scale clinical imaging, such as PET or MRI scans. Her work helps clinicians decode what their images are revealing about tumour behaviour. "We can go from the sub-cellular scale to the whole body of a mouse in preclinical imaging,” says Weigelin. “We’ve already translated some of the new PET tracers to the clinic and they have been used successfully in patients.”

One such tracer identifies a treatment stress response in tumour cells called senescence. Senescent tumour cells secrete factors involved in therapy resistance and being able to target them could transform cancer treatment. iFIT's molecular therapies team is already pursuing this and other tumour stress responses, says Zender. “We predict this will lead to superior, longer-lasting therapies.”