H. (Heleen) Vroman, MSc, PhD

Immunotherapy is a promising approach in the treatment of cancer. It tries to harness the potency and specificity of the immune system to attack cancer cells, aiming for a non-toxic treatment with minor side-effects and a long-lasting immunological memory. Various strategies can be used to boost the immune system, such as cellular strategies and checkpoint inhibitors. Within our department we have clinical trials ongoing in which patients with non-small cell lung cancer are treated with PD-1 inhibitors. Furthermore, we have developed dendritic cell (DC)-based immunotherapy to treat mesothelioma. Mesothelioma is an asbestos-induced tumor with a very poor prognosis and a median survival around 12 months after diagnosis. DC therapy to treat mesothelioma was developed in murine models, where administration of DCs loaded with tumor lysate induced potent tumor-specific CD8 T cell responses and prolonged survival. DC therapy is currently exploited in various clinical trials in both pleural as abdominal mesothelioma.

Heleen Vroman is currently a Post-Doctoral researcher within the Thorr group of the Pulmonary Medicine Department. Heleen studied biomedical sciences at Utrecht University. After her Bachelor of Science degree, Heleen finished her Master in Biology of Disease at Utrecht University. In 2012, she started her PhD project at the department of Pulmonary Medicine at the Erasmus MC in Rotterdam under the supervision of Dr. Mirjam Kool and Prof. dr. Rudi W. Hendriks. In 2017 she defended her thesis entitled: ‘Heterogeneity in Asthma; Implications for Dendritic Cell Activation?’. After obtaining her PhD, she started working as a Post-Doc in the Thorr group of the Pulmonary Medicine Department. The Thoracic Oncology research Rotterdam (Thorr) group is headed by Prof. M.D. Joachim Aerts, and is situated in the laboratory of Prof. Rudi Hendriks. Within the Thorr group both clinical research and translational research is performed with a primary focus on pulmonary oncologies as lung cancer and mesothelioma.

1. van Gulijk M, Dammeijer F, Aerts JGJV, Vroman H (2018). Combination Strategies to Optimize Efficacy of Dendritic Cell-Based Immunotherapy.
   Front Immunol. 2018 Dec 5;9:2759.
2. Aerts JGJV, de Goeje PL, Cornelissen R, Kaijen-Lambers MEH, Bezemer K, van der Leest CH, Mahaweni NM, Kunert A, Eskens FALM, Waasdorp C, Braakman E, van der Holt B, Vulto AG, Hendriks RW, Hegmans JPJJ, Hoogsteden HC (2018). Autologous Dendritic Cells Pulsed with Allogeneic Tumor Cell Lysate in Mesothelioma: From Mouse to Human.
   Clin Cancer Res. 15;24(4):766-776.
3. Dammeijer F, Lievense LA, Kaijen-Lambers ME, van Nimwegen M, Bezemer K, Hegmans JP, van Hall T, Aerts JG (2017). Depletion of Tumor-Associated Macrophages with a CSF-1R Kinase Inhibitor Enhances Antitumor Immunity and Survival Induced by DC Immunotherapy.
   Cancer Immunol Res. 5(7):535-546.
4. De Goeje PL, Smit EF, Waasdorp C, Schram MTB, Kaijen-Lambers MEH, Bezemer K, de Mol M, Hartemink KJ, Nuyttens JJME, Maat APWM, Hegmans JPJJ, Hendriks RW, Senan S, Aerts JGJV (2017). Stereotactic Ablative Radiotherapy Induces Peripheral T-Cell Activation in Patients with Early-Stage Lung Cancer.
   Am J Respir Crit Care Med. 1;196(9):1224-1227.
5. Dammeijer F, Lievense LA, Veerman GD, Hoogsteden HC, Hegmans JP, Arends LR, Aerts JG (2016). Efficacy of Tumor Vaccines and Cellular Immunotherapies in Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis.
   J Clin Oncol. 10;34(26):3204-12.

Based on previous results in animal models, three phase I/II clinical trials were performed involving mesothelioma patients, who were treated with five DC vaccinations. These trials have shown that DC therapy is safe and feasible in mesothelioma patients, and more importantly, several patients showed a reduction in tumor load, indicating efficacy of DC vaccination. This research is now continued with a phase III clinical trial in which efficacy will be compared with best standard care. DC therapy can be hampered by the strong immunosuppressive environment of the tumor, as the tumor microenvironment comprises various immune suppressive cell types, such as regulatory T cells, myeloid derived suppressor cells and tumor-associated macrophages. Therefore, in our murine mesothelioma model we are optimizing DC therapy through combination with other immunomodulatory agents that target the immunosuppressive environment of the tumor.

Figure: Overall survival and RECIST responses after first vaccination.

A. Swimmer plot of patients in phase I clinical trial with MesoPher treatment. Overall survival of patients since date of first vaccination is represented by the filled bars. Start and end of RECIST responses are depicted by the red triangles and black squares, respectively. First evaluation of response was after 6 weeks for all patients. Patients treated with chemotherapy prior to inclusion in the study are depicted with a gray diamond. The other patients were treatment naïve. B. Pre-and postvaccination CT scans of patient 5. CT scans with contrast of the ongoing response of one treatment-naïve patient receiving allogeneic lysate pulsed autologous DC vaccination. Tumor mass is indicated with pink arrows. All lesions were solid. This patient was treatment naïve and received 5 doses of 25 million DCs. Pretreatment tumor burden decreased with 70% after third vaccination (6 weeks after start of treatment) and continued to decrease (from: Aerts JGJV, et al, Clin Cancer Res. 2018).