Infection and Immunity

Nierkens

Optimizing the efficacy and safety of immunotherapy in children with cancer is the main theme of the Nierkens research group. We particularly focus on strategies to enhance immunity against pediatric acute leukemia, neuroblastoma and brain tumors, and study the function of immune cells over time in children undergoing hematopoietic cell transplantation and/or receiving immune therapy, such as CAR-T cells.

To increase anti-tumor immunity post-transplant, we developed a dendritic cell vaccine from the same graft that is used to transplant the patient. This unique approach led to a GMP-protocol and the first approved investigator-initiated cell therapy to start in the Princess Máxima Center: the U-DANCE trial. Our T cell therapy program with T cell receptor (TCR) engineered T cells and chimeric antibody receptor (CAR) T cells from different sources (peripheral or cord blood, or cultured from hematopoietic stem cells) and developed an extensive immune monitoring program to understand why some children respond well to these treatments, while others don’t.

My team works in close collaboration with Prof. Huitema on pharmacokinetic and pharmacodynamic studies to assess the association between the actual exposures of drugs used to condition the patients (e.g. ATG, fludarabine), and relevant clinical outcome parameters, such as survival, incidence of graft-versus-host, relapse, etc. We were able to find optimal exposures and adjusted the dosing regimen accordingly, which significantly increased survival chances of transplanted children. It is my strong belief that immune monitoring studies are necessary (but currently largely missing in clinical trials) to better understand the functional dynamics of the immune system in a growing child treated for cancer. Our data of the detrimental effects of combined high exposure of ATG with G-CSF on immune reconstitution post-HCT show that we can save lives even by optimizing dosing drugs already used for decades based on individual biological parameters and not only dogmatism.

To be better able to translate my findings to clinical use I got trained as a Medical Immunologist, accredited according to guidelines of the College of Medical Immunologists of the Dutch Society of Immunology (3-year residency, full time). Within the ISO15189-accredited laboratory my focus areas are the development of innovative technologies in Hemato-oncology, Immune monitoring, Cell and functional diagnostics, and Serology. I have a strong focus on translating data from fundamental studies into clinical implementation and founded the institute-wide Platform Immune Monitoring to facilitate translational research in clinically well-defined (sub)cohorts of patients suffering from cancer, inflammatory and immune-mediated diseases to study disease-overlapping immune profiles using cellular and proteome signatures. I expect that this approach will lead to a better understanding of the differences and overlapping immune profiles in patients, which will result in personalized immunotherapy approaches and drug repurposing.

As Principal Investigator Pediatric Tumor Immunology and Hematopoietic cell transplantation I am affiliated to both the Princess Máxima Center and the University Medical Center Utrecht with the mission to initiate collaborations and knowledge exchange between the two centers to stimulate the development of immune therapy for pediatric cancers. Moreover, with the composition of the Máxima Comprehensive Childhood Cancer Center (M4C) disease group HCT and immunotherapy, we bring together basic and clinical scientists and stimulate translational research.

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