Tumour-infiltrating lymphocyte (TIL) therapy have been a stable of cell therapy for many years and how recently shown clinical effect in phase III studies. How are TILs made, what are the major challenges the therapy face, and what’s next?

In this episode we are joined by Dr Özcan Met, an associated professor at Herlev og Gentofte Hospital, Center for Cancer Immune Therapy (CCIT), Copenhagen University Hospital and Technical University Denmark, who is at the forefront of TIL research.

In the episode we discuss how Dr Met and his colleagues are marrying advanced CRISPR edits with TIL therapy to knock-out PD-1, and what’s next for the field. The articles we discuss are:

1. 'Tumor-Infiltrating Lymphocyte Therapy or Ipilimumab in Advanced Melanoma’ by Rohaan MW et al, NEJM, 2022 (https://pubmed.ncbi.nlm.nih.gov/36477031/).

2. 'Highly efficient PD-1-targeted CRISPR-Cas9 for tumor-infiltrating lymphocyte-based adoptive T cell therapy’ by Chamberlain CA et al, Mol Therapy Oncolytics, 2022 (https://pubmed.ncbi.nlm.nih.gov/35141398/).

3. 'Tumour-infiltrating lymphocyte therapy comes of age in the era of genetic engineering’ by Crowther MD et al, Lancet Oncology, 2025 (https://pubmed.ncbi.nlm.nih.gov/41167225/).

4. ' Unlocking tumor-infiltrating lymphocyte potential with CRISPR-Cas9’ by Met Ö and Svane IM, Lancet Oncology, 2025 (https://pubmed.ncbi.nlm.nih.gov/40315881/).

In this episode we interview Dr. Johanna Olweus and Dr. Morten Milek Nielsen from University of Oslo about the use of T cell receptors (TCR’s) as immunotherapy against cancer.

Dr. Olweus’s group has been speadheading identifying TCRs that are specific for minute mutations in cancer cells, that can be used in adoptive T-cell-based therapies. We talk about what the therapy entails, how TCRs are discovered and go through several papers her group has published recently on using TCR-based therapies against leukemia.

The articles discussed are:

- “Induction of neoantigen-reactive T cells from healthy donors” (link: https://pubmed.ncbi.nlm.nih.gov/31101906/)

- “T cells targeted to TdT kill leukemic lymphoblasts while sparing normal lymphocytes” (Link: https://www.nature.com/articles/s41587-021-01089-x)

- “A T cell receptor targeting a recurrent driver mutation in FLT3 mediates elimination of primary human acute myeloid leukemia in vivo” (Link: https://www.nature.com/articles/s43018-023-00642-8)

- “A systematic safety pipeline for selection of T-cell receptors to enter clinical use” (Link: https://pubmed.ncbi.nlm.nih.gov/37607971/)

You can read more about Dr. Olweus research group here: https://www.ous-research.no/olweus/

In this episode we talk to Dr. Rasmus O Bak from Aarhus University about the use of CRISPR and its use in cellular therapies. CRISPR has now become a method to not only knock gene’s out but - as Dr. Bak explains - also an all-round tool that can be utilized to a variety of different task.

We discuss research from Dr. Bak’s research group, examining how CRISPRa and CRISPRi - a method to either active or inactivate genes - can be used in both hematopoietic stem cells and T cells to up- and down-regulate genes and push cells into entire new cellular states.

The articles discussed are:

• “Targeted regulation of transcription in primary cells using CRISPRa and CRISPRi” (Link: https://genome.cshlp.org/content/31/11/2120.long)
• 40-year-old associate professor is this year's recipient of the faculty's talent award (Link: https://biomed.au.dk/display/artikel/40-year-old-associate-professor-is-this-years-recipient-of-the-facultys-talent-award)
• “UK first to approve CRISPR treatment for diseases: what you need to know” (Link: https://www.nature.com/articles/d41586-023-03590-6)