Diagnostic Blood test*

The IOpener™ products, our immune-oncology diagnostic blood tests, provide timely therapy advice for cancer treatment with immune checkpoint inhibitors based on kinase activity of peripheral blood cells. Kinases play a crucial role in immune checkpoint regulation and therefore have the potential to predict a patient’s response before immune checkpoint inhibitor -ICI- treatment is started. The response to ICI treatment is driven by an individual patient’s kinase activity profile and can give key information to clinicians in support of treatment decisions. 

One of today’s greatest challenges in healthcare is to provide timely and optimal treatment for cancer patients. Despite significant advances in cancer treatment by the use of immune checkpoint inhibitors only 30-50% patients respond to these therapies. Current biomarkers are unable to provide this level of diagnostic subtlety, meaning that many patients receive suboptimal treatment resulting in a poor response, side-effects and unnecessary costs.

PamGene’s novel diagnostic blood test, the IOpener™, allows rapid measurement of protein kinase activity in Peripheral Mononuclear Blood Cells (PBMCs) from the blood of advanced stage Melanoma and Non Small Cell Lung Cancer (NCLC) patients providing a predictive score for the likelihood of the individual’s response to checkpoint inhibitor therapy.

Pamgene’s diagnostic technology will decrease the number of both over- and undertreated Melanoma and NSCLC patients, resulting in:

  • Providing the right treatment without delay
  • Saving costs by providing immunotherapy only to patients who are likely to respond
  • Improve patient outcomes and avoid unnecessary side effects

Diagnostic Development

Proof-of-concept studies, including advanced stage Melanoma and Non Small Cell Lung Cancer patients, concluded the IOpener™ to be a promising reliable predictive diagnostic for clinical response to CTLA-4 and/or PD-1 checkpoint immunotherapy. The studies concluded:

  • Kinase activity profiles of PBMC samples prior to checkpoint inhibitor therapy can predict the likelihood of response to anti-PD1 or anti-CTLA4 therapy
  • This assay may serve as a rapid and fast predictive liquid biomarker to stratify patients prior to treatment
  • Results suggest the involvement of immune cell receptor kinases as the underlying mechanism of response towards immunotherapy

Multi-center clinical studies for prospective collection of PBMC samples from anti-PD-1-treated patients in advanced stage melanoma and NSCLC are currently on going to prepare IVD accreditation for a diagnostic test of PamGene’s blood based kinome profile in patients treated with ICI.

PamGene has recently further developed the kinome biomarker technology and established the ISO13485 compliant Diagnostic Assay Services facility in order to provide kinase activity profiling as in-vitro diagnostics (IVD) assay service for the prediction of therapy response for oncological diseases from its facility in the Netherlands. Device manufacturing is performed in-house in a cleanroom and is fully scalable and transferable. PamGene’s Diagnostic Assay services facility is ISO13485:2016 complaint. 

Relevant Publications

Blood-Based Multiplex Kinase Activity Profiling as a Predictive Marker for Clinical Response to Checkpoint Blockade in Advanced NSCLC. Hurkmans, D., Verdegaal, Els, M. E.,  de Wijn, R., Koolen, S.T.W, Lamers, C., van den Heuvel, D.M.A., … , Aerts, J.G.J.V. (2019). IASLC 2019 World Conference on Lung Cancer, Abstract 1322. https://doi.org/10.1016/j.jtho.2019.08.1511
Differential Kinase Activation in Peripheral Blood Mononuclear Cells from Non-Small-Cell Lung Cancer Patients Treated with Nivolumab. Noé G, Bellesoeur A, Golmard L, Thomas-Schoemann A, Boudou-Rouquette P, Tiako Meyo M, Puszkiel A, Arrondeau J, Alexandre J, Goldwasser F, Blanchet B, Vidal M (2019). Cancers 2019, 11(6), 762.
Blood-based multiplex kinase activity profiling as a predictive marker for clinical response to checkpoint blockade in advanced melanoma. Hurkmans, D., Verdegaal, Els, M. E., Schindler, Sabrina, A., Basak, E. A., van den Heuvel, D. M. A., de Wijn, R., … van de Burg, S. H. (2018).  J. Clin. Onc, 36, Suppl. Abstracts 9579.
Differential escape mechanisms in cetuximab-resistant head and neck cancer cells. Willey CD, Anderson JC, Trummell HQ, Naji F, de Wijn R, Yang ES, Bredel M, Thudi NK, Bonner JA. Biochem Biophys Res Commun. (2019) Sep 10;517(1):36-42.
Systemic analysis of tyrosine kinase signaling reveals a common adaptive response program in a HER2-positive breast cancer. Schwill M, Tamaskovic R, Gajadhar AS, Kast F, White FM, Plückthun A. (2019) Sci Signal. Jan 22;12(565)

Profiling Activity of Cellular Kinases in Migrating T-Cells. Chirumamilla CS, Fazil MHUT, Perez-Novo C, Rangarajan S, de Wijn R, Ramireddy P, Verma NK, Vanden Berghe W.n (2019) Methods Mol Biol. ;1930:99-113

The ALK inhibitor AZD3463 effectively inhibits growth of sorafenib-resistant acute myeloid leukemia. Moharram SA, Shah K, Khanum F, Rönnstrand L, Kazi JU. (2019) Blood Cancer J. Jan 15;9(2):5
Inactive immune pathways in triple negative breast cancers that showed resistance to neoadjuvant chemotherapy as inferred from kinase activity profiles. Sawada T, Hilhorst R, Rangarajan S, Yoshida M, Tanabe Y, Tamura K, Kinoshita T, Shimoyama T, van Beuningen R, Ruijtenbeek R, Tsuda H, Koizumi F. (2018) Oncotarget. Sep 28;9(76):34229-34239.

Ex vivo multiplex profiling of protein tyrosine kinase activities in early stages of human lung adenocarcinoma
Arni S, Nhung Le TH, de Wijn R, Garcia-Villegas R, Dankers M, Weder W and Hillinger S (2017). Oncotarget Aug 2;8(40):68599-68613

* For Research Use Only, not for use in diagnostic procedures