Link to paper

van de Donk PP, Kist de Ruijter L, Lub-de Hooge MN, Brouwers AH, van der Wekken AJ, Oosting SF, Fehrmann RSN, de Groot DJA, de Vries EGE

Immune checkpoint inhibitors (ICIs) have substantially changed the field of oncology over the past few years. ICIs offer an alternative treatment strategy by exploiting the patients’ immune system, resulting in a T cell mediated anti-tumor response. These therapies are effective in multiple different tumor types. Unfortunately, a substantial group of patients do not respond to ICIs. Molecular imaging, using single-photon emission computed tomography (SPECT) and positron emission tomography (PET), can provide non-invasive whole-body visualization of tumor and immune cell characteristics and might support patient selection or response evaluations for ICI therapies. In this review, recent studies with 18F-fluorodeoxyglucose-PET imaging, imaging of immune checkpoints and imaging of immune cells will be discussed. These studies are until now mainly exploratory, but the first results suggest that molecular imaging biomarkers could have a role in the evaluation of ICI therapy.

On Monday February 24th, Kirsten Moek successfully defended his PhD thesis. See the summary description of his thesis below:

Over the last decades many molecules and key pathways in cancer were identified, which facilitated a shift in anticancer drug development from DNA-damaging chemotherapy to a more personalized approach with targeted antibody therapeutics including antibody-drug conjugates (ADC) and bispecific T-cell engagers (BiTEs). A major challenge in oncology is to identify those patients that will benefit from targeted antibody therapeutics. Eventually this should lead to ‘personalized medicine’ in which a specific drug is used to treat a tumor with specific molecular or genetic characteristics in a specifically selected patient. Therefore, it is important to assess tumor selective expression of molecular targets, which is usually done by immunohistochemistry (IHC), but there may also be a role for molecular PET imaging in selecting patients and predicting tumor responses. This thesis provides an overview of molecular PET imaging with antibodies in cancer patients. Moreover, results from a first-in-human PET study using a BiTE as tracer were published. With a plethora of targeted agents becoming available to treat patients with cancer, broad knowledge concerning frequency of target expression across tumor types is of importance to fully exploit therapeutic options. Performing large-scale, golden standard, IHC analyses for many drug targets is time-consuming and demands many resources. Therefore we used functional genomic mRNA profiling instead to predict target overexpression rates for the proteoglycan “glypican 3” and for 59 ADC targets across 60 tumor types and subtypes.

Link to paper

Bhattacharya A, Bense RD, Urzúa-Traslaviña CG, de Vries EGE, van Vugt MATM, Fehrmann RSN

Abstract
Copy number alterations (CNAs) can promote tumor progression by altering gene expression levels. Due to transcriptional adaptive mechanisms, however, CNAs do not always translate proportionally into altered expression levels. By reanalyzing >34,000 gene expression profiles, we reveal the degree of transcriptional adaptation to CNAs in a genome-wide fashion, which strongly associate with distinct biological processes. We then develop a platform-independent method—transcriptional adaptation to CNA profiling (TACNA profiling)—that extracts the transcriptional effects of CNAs from gene expression profiles without requiring paired CNA profiles. By applying TACNA profiling to >28,000 patient-derived tumor samples we define the landscape of transcriptional effects of CNAs. The utility of this landscape is demonstrated by the identification of four genes that are predicted to be involved in tumor immune evasion when transcriptionally affected by CNAs. In conclusion, we provide a novel tool to gain insight into how CNAs drive tumor behavior via altered expression levels.