Program
14:30-15:05 Magnus Essand, PhD. Prof of Gene Therapy, Uppsala University. Co-founder and Chief Scientific Officer of Elicera Therapeutics "Arming CAR-T cells for potent bystander anti-tumor immune responses"
15:05-15:25 Coffee break with refreshments
15:25-16:00 Anna Dimberg, PhD. Professor of Cancer and Vascular Biology, Uppsala University: "Tailoring vascular phenotype to induce anti-tumor immunity"
Abstract Essand
Essand will briefly present Uppsala’s experiences from academic clinical trials with chimeric antigen receptor (CAR)-T cells and then focus on the development of next generation CAR-T cells for the treatment of solid tumours.
Main challenges with CAR-T cell therapy of solid tumours include antigen heterogeneity and immune suppression. Thus, next generation CAR-T cells must be able to withstand or reduce immune suppression within tumours and induce epitope spread with activation of T cells towards whatever neoepitope a tumour contains.
CAR-T cells armed with the neutrophil-activating protein (NAP) from Helicobacter Pylori can attract dendritic cells to take up and present tumour-associated antigens to CD8 T cells, which will then mount an attack on tumour cells, independently whether they express the antigen targeted by the CAR or not. Clinical adaptation of CAR(NAP)-T cell production in the closed and automated Prodigy system (Miltenyi) will be discussed and two upcoming CAR-T clinical trials, for patients with B cell lymphoma and glioblastoma, will be presented.
Abstract Dimberg
Glioblastomas (GBMs) are aggressive brain tumors which are resistant to immunotherapy. This is partly due to the immunosuppressive tumor microenvironment (TME) and the dysfunctional tumor vasculature, which hinder T cell infiltration. There are several ways to target the vasculature to improve cancer immunotherapy, including anti-angiogenic therapy, blocking immunosuppressive feed-back loops in endothelial cells or inhibiting proteins expressed on tumor endothelial cells that reduce endothelial activation. An alternative strategy is to instead stimulate tumor endothelial cells to transform to high endothelial venules (HEV), which may also lead to formation of tertiary lymphoid structures (TLS).
The role of HEVs and TLS in regulating the immune microenvironment in GBM will be discussed, as well as our experiences in inducing these structures therapeutically in pre-clinical glioma models. Our work reveals that altering vascular phenotype can promote efficient anti-tumor T cell responses and prolong survival in glioma. This has broader implications for treatment of other immunotherapy-resistant tumors.
Biosketches
Magnus Essand obtained his PhD at Uppsala University, Uppsala, Sweden in 1995 and his postdoctoral training at the National Cancer Institute, Bethesda, USA. He returned to Sweden in 2000, first as an Associate Professor and from 2009 as a full Professor at the Department of Immunology, Genetics and Pathology, Uppsala University. Essand has tutored twelve PhDs to completion of their doctoral thesis and is currently the main supervisor of three PhD students and six postdocs. He has published 98 original peer-reviewed scientific research articles and 14 review articles. Research activities in Essand’s group concern tumour immunology and immunotherapy of cancer, focusing on the development of chimeric antigen receptor (CAR)-T cells, viral vectors, and oncolytic viruses with the ability to induce bystander immune responses. Most of the work is preclinical but some developments have entered clinical evaluation. Essand is currently sponsor’s representative for two early phase clinical trials; One trial treating neuroendocrine cancer patients with an oncolytic virus; and one trial treating B-cell lymphoma patients with CAR-T cells. Clinical translation of armed CAR-T cells developed in Essand’s laboratory are underway both for B-cell lymphoma and glioblastoma.
Anna Dimberg received her PhD in 2002, investigating molecular mechanisms regulating differentiation in hematopoietic malignancies. She entered the vascular biology field as a postdoctoral fellow, and became an Associate Professor in Experimental Pathology at Uppsala University in 2009. She is Professor of Cancer and Vascular Biology at the Department of Immunology, Genetics and Pathology, Uppsala University since 2021. The aim of her research is to understand how vessel phenotype is altered in tumors, and how the abnormal vasculature affects the tumor microenvironment and the response to different types of cancer therapy. A main interest is to investigate how differential gene expression in tumor endothelial cells affects immune response and tumor progression. The long-term goal is to to identify vascular targeting strategies that can be used to improve the response to cancer therapy, including immunotherapy.