M. (Marcella) Willemsen MSc, PhD

Studying how to initiate an effective anti-tumor immune response: role of vaccination

Immunotherapy in the form of immune checkpoint inhibition is an integral part of the treatment of lung cancer and other malignancies. However, the mortality rates remain high. Therefore, there is a critical need to further harness the power of the immune system and expand treatment options. The Department of Pulmonary Medicine of the Erasmus MC has developed a dendritic cell-based immunotherapy for the treatment of malignant mesothelioma, that has evolved from bench to bedside. Currently, this treatment is being optimized and studied in malignancies other than mesothelioma, which are not limited to pulmonary malignancies, including pancreatic cancer. At the same time, the group is working on development of biomarkers that predict the response to treatment beforehand or early on-treatment. This will lead to methods that can be exploited in clinical setting in order to decide which patients will benefit from specific treatment, thereby facilitating personalized treatment and preventing overtreatment and unnecessary side effects.

After obtaining her bachelor degree in Health and Life Sciences and her master degree in Oncology at the VU Amsterdam, she performed her PhD studies at the department of Dermatology at the Amsterdam University Medical Centers under de guidance of Prof. dr. Rosalie Luiten and Prof. dr. Marcel Bekkenk. She investigated the balance between autoimmunity and immune escape in the context of vitiligo and melanoma. After obtaining her PhD in 2022, she started as a postdoctoral researcher at the Department of Pulmonary Medicine, Erasmus MC, to study immunomodulatory effects of immunotherapy in patients with solid cancers.

1. Aerts JG, Belderbos R, Baas P, Scherpereel A, Bezemer K, Enninga I, Meijer R, Willemsen M, Berardi R, Fennell D, Kerstens R, Cornelissen R, van Meerbeeck JP; DENIM team. Dendritic cells loaded with allogeneic tumour cell lysate plus best supportive care versus best supportive care alone in patients with pleural mesothelioma as maintenance therapy after chemotherapy (DENIM): a multicentre, open-label, randomised, phase 2/3 study. Lancet Oncol. 2024 Jul;25(7):865-878. doi: 10.1016/S1470-2045(24)00191-8. Epub 2024 Jun 4. PMID: 38848742.
2. van 't Land FR, Willemsen M, Bezemer K, van der Burg SH, van den Bosch TPP, Doukas M, Fellah A, Kolijn PM, Langerak AW, Moskie M, van der Oost E, Rozendaal NEM, Baart SJ, Aerts JGJV, van Eijck CHJ. Dendritic Cell-Based Immunotherapy in Patients With Resected Pancreatic Cancer. J Clin Oncol. 2024 Sep 10;42(26):3083-3093. doi: 10.1200/JCO.23.02585. Epub 2024 Jul 1. PMID: 38950309; PMCID: PMC11379361.
3. Dietz MV, Quintelier KLA, van Kooten JP, de Boer NL, Vink M, Brandt-Kerkhof ARM, Verhoef C, Saeys Y, Aerts JGJV, Willemsen M, Van Gassen S, Madsen EVE. Adjuvant dendritic cell-based immunotherapy after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in patients with malignant peritoneal mesothelioma: a phase II clinical trial. J Immunother Cancer. 2023 Aug;11(8):e007070.
4. van Eijck CWF, Haddaoui HE, Kucukcelebi S, Vadgama D, Fellah A, Mustafa DAM, Aerts JGJV, van Eijck CHJ, Willemsen M. Rintatolimod in Advanced Pancreatic Cancer Enhances Antitumor Immunity through Dendritic Cell-Mediated T-Cell Responses. Clin Cancer Res. 2024 Aug 15;30(16):3447-3458. doi: 10.1158/1078-0432.CCR-23-4085. PMID: 38488815.
5. van Eijck CWF, Strijk G, Vietsch EE, van der Sijde F, Verheij M, Mustafa DAM, Vink M, Aerts JGJV, van Eijck CHJ, Willemsen M. FOLFIRINOX chemotherapy modulates the peripheral immune landscape in pancreatic cancer: Implications for combination therapies and early response prediction. Eur J Cancer. 2024 Jan;196:113440. doi: 10.1016/j.ejca.2023.113440. Epub 2023 Nov 17. PMID: 37988843. 
6. Belderbos RA, Corneth OBJ, Dumoulin D, Hendriks RW, Aerts JGJV, Willemsen M. Atypical B cells (CD21-CD27-IgD-) correlate with lack of response to checkpoint inhibitor therapy in NSCLC. Eur J Cancer. 2024 Jan;196:113428. doi: 10.1016/j.ejca.2023.113428. Epub 2023 Nov 

We have recently demonstrated that vaccination with autologous dendritic cells pulsed with allogeneic tumor cell lysate led to systemic immune cell activation and had the potential to initiate tumor-lysate specific immune responses. The current focus is to improve tumor-lysate specific T cell infiltration in the tumor and/or metastasis, for which combination therapy appears to be needed. Furthermore, we are studying novel approaches for (personalized) vaccination. In addition, we have identified immune cell characteristics that underlie clinical efficacy of immunotherapy or chemotherapeutic agents in mesothelioma and pancreatic cancer. The selected publications below give an impression of our work.