About
the Principal Investigator - Victor Peperzak

Career and academic achievements
Throughout my academic career, my research has consistently been at the intersection between the adaptive immune system and cancer therapy, between B cell malignancies and T cell biology, and between basic research and clinical implementation. My PhD at the Dutch Cancer Institute (NKI) was focussed on T cell co-stimulation and was followed by postdoctoral research at the Walter and Eliza Hall Institute (WEHI) in Australia. Here, I focussed on regulation of pro-survival proteins in germinal center B cells and plasma cells. This work was supported by an EMBO long-term fellowship (2010-2012), a personal grant from the American multiple myeloma research foundation (MMRF, 2011-2013) and the ‘2012 New Investigator Award’ from the Australian and New Zealand Society for Immunology (ASI). This research line was continued in the context of B cell malignancies during a second postdoc at the AMC in Amsterdam and supported by an NWO-Veni grant (2013-2016). Receiving a follow-up 6-year personal young investigator grant from the Dutch Cancer Society (KWF, 2016-2022) allowed me to established my own research group at the UMC Utrecht (UMCU) in 2016.
Based on previous scientific interests I developed two main research lines; 1) targeting malignant B cells to improve patient treatment and 2) designing a modified killing machinery to improve cellular immunotherapy. In addition to abovementioned personal grants I received multiple project grants from the KWF, Alpe d’HuZes and Lymph&co, and received funding from collaborations with industry to execute different research projects within these research lines.

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Vision
Although major scientific breakthroughs, such as immunotherapy and organoid technology, were heralded as game-changers for the treatment of cancer there is still a large patient group unable to benefit from these technologies. My vision is to narrow the gap between scientific discoveries and clinical application. I aim to achieve this by further investing in collaborations with clinicians as well as (fundamental) scientists and bridge the gap between what is clinically needed and what is technically possible.
One example of my dedication towards this goal is based on the finding that inhibitors of MCL-1, an essential target in multiple myeloma (MM), resulted in dose-dependent cardiac toxicity in patients, limiting effective treatment. Thanks to long-term collaborations that I have established with hematologists at the UMCU, and by using patient material, my team discovered multiple ways that enable lowering the dose of MCL-1-inhibitors, reduce MCL-1 expression or target MCL-1 in cancer cells specifically. Some of our findings have already been incorporated in new clinical trial design for MM.
A second example is the effort I have put in generating predictive 3D culture models with patient cells. These culture models are in many ways superior to using human cell lines or xenograft mouse models. Using these 3D models we have published articles on synergistic drug combinations for MM, shown the added benefit of sequential drug treatment and revealed a culture setting that predicts clinical responses to CD38-targeting antibody daratumumab. Our 3D models form the basis of work packages in multiple awarded KWF projects on MM and classical Hodgkin lymphoma (HL), and underlies my participation as PI in the Oncode-Accelerator consortium, that is aimed at efficient development and clinical validation of novel cancer therapies.
A third example is based on the fact that cellular immunotherapy using chimeric antigen receptor (CAR) T cells is often characterized by primary resistance and cancer relapse. My team developed and patented optimized killing (OK) technology (WO2023/031215A3) that boosts tumor cell killing by CAR T or NK cells and improves anti-tumor responses. Ultimately, my combined work will improve personalized treatment and diagnosis of patients suffering from B cell cancers and enhance efficacy of cellular immunotherapy.