Emile Voest, MD, Ph.D.Professor of Medical Oncology, Medical Director of the NKI
About Emile Voest
Immunotherapy, genomics and (tumor)organoids
We recently published a very exciting translational study to
generate better understanding of which tumors are recognized by T
cells (Dijkstra et al. Cell, 2018). In this set of experiments we
used autologous organoids to induce an immune response on PBMC. In
colorectal cancer and NSCLC we have seen PBMC responses when
exposed to autologous tumor organoids. These T cells can be
expanded for further research and even in the future for T cell
treatment. This creates a very interesting platform and studies are
underway to better understand resistance to the immune system.
Several trials and translational studies are ongoing. The NICHE
trial is a unique study that investigates the use of neoadjuvant
immunotherapy in colorectal cancer. First results are now coming in
which allows the assessment of safety and initial outcome. We also
invested a great deal of time and energy in obtaining paired
biopsies from melanoma or lung patients treated with immunotherapy.
Large scale efforts to analyze WGS data of >100 patients treated
with immunotherapy and for whom we have clinical outcome data are
underway. These data are subsequently compared with the data set of
paired biopsies of patients treated with immunotherapy.
Furthermore, we have used computational biology to investigate the
true value of mutual exclusivity (van der Haar et al. Cell,
Genomic guided personalized medicine
We have created a data base of almost 5000 patients with
metastatic cancer (of any kind) underwent biopsies to obtain fresh
tumor material at the start of new systemic treatment and were
whole genome sequenced (WGS) in conjunction with clinical outcome
data. The NKI alone has contributed >1000 patients to this
unique Dutch data set. I am very excited that, in collaboration
with HMF, in 2019 all patients of the NKI will have access to WGS,
an unprecedented step in the implementation of precision medicine
which will undoubtedly further our knowledge.
We continue the Drug Rediscovery Protocol, in short DRUP. In
this multi-pharma (12 companies to date), multi-drug (26 drugs to
date), multi-center (30 centers to date) study we now have created
a platform through which patients can get access to approved
medication based on a genomic profile coupled to a tumor type.
These drugs are provided for free by pharma and the number of drugs
and hospitals are expanding. In the first analysis we have
encountered a clinical benefit ratio (defined as complete or
partial remission or stable disease >16 weeks) of ~30%. This is
surprisingly high and reflects that patient selection is key in
such a personalized medicine approach.
Organoids as a tool to personalize medicine
Finally, in the context of our personalized medicine efforts we
have investigated whether organoids derived from tumors from
individual patients have the capacity to predict treatment
responses. We have initiated several clinical trials to investigate
the value of these organoids as predictive tools. These trials
include validation studies in patients with chemotherapy and
targeted therapy in lung and colorectal cancer (TUMOROID),
organoid-guided experimental treatment studies (SENSOR) and more.
We have now shown that tumor organoids can predict
non-responsiveness to irinotecan-based chemotherapy but not to
In summary, my group is strongly committed to develop a better
understanding of individual tumors and their responsiveness to
immunotherapy and targeted /chemotherapy. By combining basic
research with translational studies we are successful in
bringing novel findings very quickly to patients.