Sabrina Oliveira obtained her PhD in Targeted Cancer Therapies at the department of Pharmaceutical Sciences of Utrecht University (2004-2008). Thereafter, she worked as a postdoc on the development of tracers based on nanobodies for optical molecular imaging, at the department of Biology (2009-2011). In 2012, she was awarded a VENI grant from the Netherlands Organization for Research (NWO-STW), with which she started her own research line, with the goal to render photodynamic therapy cancer-specific, by targeting the photosensitizer to cancer cells using nanobodies. In 2016, she received a Starting Grant from the European Research Council to expand that research and start her own group. Currently, she is an Associate Professor, with a shared position between the department of Biology and the department of Pharmaceutical Sciences. She is very interested in rendering therapies more specific using nanobodies  and eager to bring these as close as possible to the clinic.

Nanobodies are well known for their small dimensions and high binding affinities to their targets, which lead to rapid tumor accumulation, homogenous distribution, and rapid clearance of unbound fractions. We took advantage of these properties and have developed an alternative approach for photodynamic therapy (PDT) by conjugating photosensitizers to nanobodies. Conventional photosensitizers are very hydrophobic and have limited selectivity to tumors, thus leading to normal tissue damage in the illuminated area. Notably, with nanobody-targeted PDT, cytotoxicity is selectively induced in cells which have high target expression level. Preclinical studies have shown selective tumor destruction and significant tumor regression after a single treatment session. Similar to conventional PDT, we have shown that nanobody-targeted PDT can stimulate the immune cells. More recently, we have investigated the immune responses triggered by our treatment in immunocompetent mice, where we see that also distant lesions, that are not illuminated, can respond to this therapy. This presentation will summarize these studies and discuss preliminary data obtained from testing this treatment in the veterinary clinic, in cats that are diagnosed with oral squamous cell carcinoma. Finally, brief examples will be given on additional approaches using nanobodies for targeted cancer therapy.

Prof. Dr. Jurgen Kuball
University Medical Center Utrecht

Prof. Dr. Jürgen Kuball received his medical degree as hematologists at the University of Mainz, Germany, and was further trained at the Fred Hutchinson Cancer Center in Seattle, WA, USA. Prof. Kuball joined the Department of Hematology at the University Medical Center in Utrecht in The Netherlands in 2007 as hematologists and immunologist. He became a VIDI-laureate in 2010 and chairs the section applied & tumor-immunology within the laboratory of translation immunology. Since 2013 he is chairing the Department of Hematology (adults). His clinical activities are focusing on treating patients with hematological malignancies including stem cell transplantation. His clinical-translational efforts and patient care are driven by his role as Director of the Bone Marrow Transplantation Program at the University Medical Center Utrecht, as well as active membership of the leukemia working party and stem cell working party of HOVON. His current laboratory activities are focusing on the understanding of innate immune cells and their receptors to recognize malignant cells and virally infected cells as well as the genetic engineering of a transplant.

Translational research activities of Jurgen Kuball are placed in the Kuball Laboratories. Kuballs main interested is in harnessing the immune system's natural power for therapeutic uses involves advanced genetic engineering of innate immune cells or isolating specific receptors from these cells. This strategy is key to unlocking the immune system's full therapeutic potential, specifically by creating an imbalance between activating and inhibitory receptors. A prime example is the use of receptors from γδT cells, which have an exceptional ability to identify and attack a broad range of tumor cells, even those with minimal mutations, while leaving healthy cells unharmed ¹. By harvesting these receptors, researchers can develop a novel category of engineered immune cells, known as TEGs (αβT cells engineered with a specific γδT cell receptor). This method merges the strengths of αβT cells with those of γδT cells, offering precise targeting of cancer cells without the collateral damage associated with conventional cancer therapies like chemotherapy and radiation. Moreover, genetically modifying γδT cells presents a promising strategy ². Recently, dual-targeting strategies have emerged as more adaptable and potentially more effective than some treatments in early clinical trials. These strategies employ a primary activation signal alongside a secondary co-stimulatory signal to finely tune activation, thereby avoiding immune cell exhaustion—a frequent drawback of certain therapies that can diminish their long-term effectiveness. Research into the molecular dynamics of these engineered immune cells has provided valuable insights into making them more resilient and less prone to exhaustion ³. Modifying the cells' reaction patterns can result in immune cells that have the power to maintain tumor control over extended periods.

Dr. Yanling Xiao
Leiden University Medical Center