dr. Sandra Van Lint (PhD)
Postdoctoral researcher - Thoracic Tumor Immunology Laboratory - Department of Pulmonary Medicine - UZ/UGent
Senior post-doctoral fellow of the Foundation against Cancer
Principal investigator: prof. Karim Vermaelen (MD, PhD)
Research focus
Lung cancer is a highly prevalent and lethal malignancy. The majority of lung cancer patients are diagnosed at the metastatic stage and due to drug resistance high relapse rates, 5 year overall survival is around 5%.
In the recent years, immune checkpoint blockers (ICB), acting by blocking receptor ligand interactions that cause exhaustion of tumor killer T cells, have revolutionized standard-of-care for several cancer indications. One of the best success stories is non-small cell lung cancer (NSCLC), however only a minority of patients respond, and those who do respond eventually experience disease relapse.
ICB fix only a late step in the chain of events leading to T cell induced tumor destruction (as referred to in the cancer-immunity cycle). Upstream of this is a complex process of tumor antigen uptake, processing and presentation by dendritic cells (DCs). Indeed, DCs perform several critical steps in cancer immunotherapy. However, the overwhelming majority of endogenous DCs are dysfunctional. DC-based immunotherapy aims to replace a critical system that is inherently defective in cancer patients.
We are currently exploring the therapeutic potential of immunostimulatory DCs, generated ex vivo from patient blood as a vaccine regimen for NSCLC patients. Two first-in-human clinical trials in patients affected with NSCL have recently been completed.
My research at the Thoracic Tumor Immunology Lab of the Dept. of Pulmonary Medicine will further focus on ways to re-engineer DCs in order to make our next-generation DC vaccine. We developed a target discovery platform based on i) in silico prediction; ii) in vitro screening and ii) in vivo evaluation in a humanised mouse model. With this, proof-of-concept can be validated and mechanisms of action can be unraveled.
In addition, I will further focus on the use of mRNA to reprogram immune cell behaviour and ignite the tumor microenvironment.
Biography
Sandra Van Lint obtained the certificate Biomedical Laboratory Technology, specialization in Pharmacological and Biological Techniques in 2005. In 2007, she graduated as engineer / master in the Industrial Sciences, specialization Biochemistry after which she started her scientific career at the Vrije Universiteit Brussel (VUB), Belgium. Particularly interested in immunotherapy and tumor biology, she additionally followed an Immunology and oncology course at the VUB. Later on, she obtained a PhD in medical sciences with a focus on the use of mRNA as an immunotherapeutic and medicinal product in the treatment of cancer. During her PhD, she gained particular interest in dendritic cells, cytotoxic T lymphocyte interplay and activation as well as mRNA-based immunotherapy. Moreover, particular attention was given to the suppressive tumor microenvironment and cells involved in here. In 2015, she joined the AcTakine team of the Cytokine Receptor Lab at UGent/VIB as a post-doctoral researcher to further continue and explore her interest in immunology and the development of immunotherapeutics and (cancer-) vaccines.
From January 2021, Sandra became lead scientist at the Thoracic Tumor Immunology Laboratory, focusing on mRNA-based dendritic cell vaccination for the treatment of lung cancer as well as on the use of mRNA to reprogram immune cell behaviour and ignite the tumor microenvironment. Currently, Sandra is a senior post-doctoral fellow of the Foundation against Cancer.
Key publications
- A bispecific Clec9A-PD-L1 targeted type I interferon profoundly reshapes the tumor microenvironment towards an antitumor state, Molecular Cancer, 2023 (PMID: 38031106)
- mRNA in cancer immunotherapy: beyond a source of antigen, Molecular Cancer, 2021 (PMID: 33658037)
- The opposing effect of type I interferon on the T cell response elicited by non-modified mRNA-lipoplex vaccines is determined by the route of administration, Molecular Therapy – nucleic acids, 2020 (PMID: 33230442)
- Nanoparticle-conjugated TRL7/8 agonist localized immunotherapy provokes safe antitumoral responses, Advanced Materials, 2018 (PMID: 30276880)
- Treatment with mRNA coding for the necroptosis mediator MLKL induces antitumor immunity directed against neoantigens, Nature Communications, 2018 (PMID: 30143632)
- Delivering Type I interferon to dendritic cells empowers tumor eradication and immune combination treatments, Cancer Research, 2018 (PMID: 29187401)
- Intratumoral delivery of TriMix mRNA results in T cell activation by cross-presenting dendritic cells, Cancer Immunology Research, 2016 (PMID: 26659303)
- Enhanced suppressive capacity of tumor-infiltrating myeloid-derived suppressor cells compared with their peripheral counterparts, International Journal of Cancer, 2014 (PMID: 23983191)
- Priming of Cytotoxic T Lymphocyte Responses by Dendritic Cells: Induction of Potent anti-Tumor Immune responses, Cytotoxic T lymphocytes: Mechanisms, Development and Disease, Nova Science Publishers, 2013 (ISBN 978-1-62417-328-8)
- Pro-inflammatory characteristics of SMAC/DIABLO-induced cell death in anti-tumor therapy, Cancer Research, 2012 (PMID: 22379024)
- Preclinical evaluation of TriMix and antigen mRNA-based antitumor therapy, Cancer Research, 2012 (PMID:22337996)
Contact & links
- Lab address: MRB2 2nd floor, Ghent University Hospital, Corneel Heymanslaan 10, 9000 Ghent
- Sandra Van Lint is interested to receive invitations for presentations or talks