The TCR Therapy Revival: Engineering T cells with WT1-specific receptors to fight haematological and solid malignancies

T cell receptor (TCR) cell therapy was once placed on the sidelines of onco-immunotherapy. Not only did researchers need to identify high-avidity, specific T cell receptors from the cells of healthy donors or patients, but they also had to generate complex genetic edits in T cell DNA to avoid the generation of mispaired receptors with unknown and potentially harmful specificities. With previous gene-editing technologies, this was an insurmountable challenge.

The discovery of CRISPR has led to a recent revival of TCR therapy, owing to its ability to perform multiple complex edits in human cells with relative ease. Recent research carried out by Professor Chiara Bonini's team at the Ospedale San Raffaele Scientific Institute in Italy, in collaboration with Intellia Therapeutics, led to the discovery of a TCR that is specific for Wilm’s tumour antigen 1 (WT1), the expression of which is strongly linked to the onset of cancer. They then took advantage of CRISPR-Cas9 gene-editing technology to create multiple edits in T cells to test various WT1-targeting TCRs, with promising tumour-killing results across a range of cancer types.

What will you learn from this webinar:

• Hunting anti-tumour T cell receptors
• Engineering T lymphocytes to re-address their specificity towards the tumour
• Selection and validation of the best performing anti-tumour T cell receptor

Tentative Webinar Programme:

• 15.00 Welcome and introduction by CRISPR Medicine News
• 15.05 Eliana Ruggiero, PhD, Ospedale San Raffaele Scientific Institute, Milan, Italy | The TCR Therapy Revival: Engineering T cells with WT1-specific receptors to fight hematological and solid malignancies
• 15.50 Q & A with Eliana Ruggiero
• 16.25 Close by CRISPR Medicine News

Speaker | Title:

Eliana Ruggiero, PhD, Ospedale San Raffaele Scientific Institute, Milan, Italy | The TCR Therapy Revival: Engineering T cells with WT1-specific receptors to fight haematological and solid malignancies

CMN interview

Eliana Ruggiero, PhD, Ospedale San Raffaele Scientific Institute, Milan, Italy

Dr. Eliana Ruggiero received her Ph.D. in Biology from the University of Heidelberg “Ruprecht-Karls-Universität Heidelberg” (Germany) in 2013, trained at the laboratory of Christof von Kalle. She focused her research on the exploitation of sequencing technologies for the characterisation of the T cell receptor (TCR) repertoire. She studied the distortions in the immune repertoire occurring upon infections and in tumours, with particular focus on the overtime clonal tracking of individual clonotypes. In 2015, she joined Chiara Bonini’s lab at San Raffaele Scientific Institute in Milan (Italy) with the aim of identifying new tumour-specific TCRs to be used in TCR-based immunotherapeutic approaches for several tumour entities. Her work has so far resulted in more than 30 publications in peer-reviewed journals and 3 patents.

For the recognition of her scientific achievements, she has received several awards (ASGCT Excellence in Research Award, World Immunotherapy Council Young Investigator 2019) and international fellowships (International Cancer Research Fellowship iCARE, H2020 Marie Skłodowska-Curie Individual Fellowships). Her research has been supported by the Italian Ministry of Health.

Read our CMN interview with Dr. Ruggiero from May 2022.