Lab
Johanna Olweus's Lab
Institution: Oslo University Hospital
About the lab
Our group aims to develop new T-cell based concepts for cancer immunotherapy that overcome the major challenge of self-tolerance in cancer. To this end, one of our main strategies involves studies of how the immune system from healthy donors can target patient cancer cells. We have a strong focus on the development of new technologies that allow high-throughput identification of therapeutic targets that can evoke immune responses, as lack of immunogenic targets represents a major limitation in therapeutic efficacy. The group furthermore has a strong translational focus and performs penetrating mechanistic analyses in clinical trials together with our clinical partners.
Research area 1: Target
Research area 2: Targeting of self-antigens
Research area 3: Profiling of T-cell receptors
Research area 1: Target
Research area 2: Targeting of self-antigens
Research area 3: Profiling of T-cell receptors
Featured research (1)
The identification of immunogenic neoantigens and their cognate T cells represents the most crucial and rate-limiting steps in the development of personalized cancer immunotherapies that are based on vaccination or on infusion of T cell receptor (TCR)-engineered T cells. Recent advances in deep-sequencing technologies and in silico prediction algorithms have allowed rapid identification of candidate neoepitopes. However, large-scale validation of putative neoepitopes and the isolation of reactive T cells are challenging because of the limited availablity of patient material and the low frequencies of neoepitope-specific T cells. Here we describe a standardized protocol for the induction of neoepitope-reactive T cells from healthy donor T cell repertoires, unaffected by the potentially immunosuppressive environment of the tumor-bearing host. Monocyte-derived dendritic cells (DCs) transfected with mRNA encoding candidate neoepitopes are used to prime autologous naive CD8 ⁺ T cells. Antigen-specific T cells that recognize endogenously processed and presented epitopes are detected using peptide–MHC (pMHC) multimers. Single multimer-positive T cells are sorted for the identification of TCR sequences, after an optional step that includes clonal expansion and functional characterization. The time required to identify neoepitope-specific T cells is 15 d, with an additional 2–4 weeks required for clonal expansion and downstream functional characterization. Identified neoepitopes and corresponding TCRs provide candidates for use in vaccination and TCR-based cancer immunotherapies, and datasets generated by this technology should be useful for improving algorithms to predict immunogenic neoantigens. © 2019, The Author(s), under exclusive licence to Springer Nature Limited.