Unravelling the immunotherapeutic potential of CD70 as a target in solid malignancies

BJMO - volume 13, issue 2, march 2019

J. Jacobs PhD, T. Flieswasser MSc, F. Lardon PhD, E. Smits PhD, P. Pauwels MD, PhD


Under normal conditions, CD70, member of the tumour necrosis factor family, is only transiently expressed on activated T and B cells. Instead, constitutive expression of CD70 has been described on malignant cells in a range of solid and haematological malignancies. Through its receptor, CD27, the expression of CD70 can facilitate evasion of the immune system by three important mechanisms: induction of T cell apoptosis, T cell exhaustion and increasing the amount of suppressive regulatory T cells. The general aim of this thesis was to investigate the role of CD70 in solid tumour types and explore promising combination strategies for anti-CD70 therapy. Thereby, we focused on the role of CD70 in non-small cell lung cancer and colorectal cancer.

(BELG J MED ONCOL 2019;13(2):54–59)

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Targeted therapy for the treatment of head and neck squamous cell carcinomas: hopes and pitfalls

BJMO - volume 9, issue 5, september 2015

C. Boeckx PhD, M. Baay PhD, F. Lardon PhD, J.B. Vermorken MD, PhD

Targeted therapy is a promising strategy for the treatment of head and neck squamous cell carcinoma and other cancers, which has been developed as a result of breakthroughs in molecular characterisation of carcinogenesis. It is thought to offer a higher therapeutic index and, therefore, to be associated with less toxicity than cytotoxic drugs. Unfortunately this kind of therapy also has weaknesses; in particular the long-term response rate is disappointing. This review will not only focus on the benefits of EGFR targeted agents in head and neck squamous cell carcinoma, but will also summarise its weaknesses.

(BELG J MED ONCOL 2015;9(5):175–78)

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Biomarkers for an effective and cost-effective use of anti-EGFR biotherapeutics for the treatment of head and neck cancer

BJMO - volume 9, issue 2, may 2015

C. Boeckx PhD, M. Baay PhD, F. Lardon PhD, J.B. Vermorken MD, PhD

As the epidermal growth factor receptor is expressed in up to 90% of all head and neck squamous cell carcinomas and initiates important signalling pathways in carcinogenesis, this receptor has emerged as a promising therapeutic target. Nevertheless, the challenge of drug resistance alongside treatment with epidermal growth factor receptor inhibitors remains. New results from our research group provide evidence that the RAS-MAPK signalling pathway is still activated despite upstream epidermal growth factor receptor blocking by cetuximab, an epidermal growth factor receptor targeting monoclonal antibody. DUSP5, DUSP6, AURKB, HB-EGF, IL8 and the transcription factor AP-1 were among the genes identified by us as likely contributing to cetuximab resistance. These novel findings provide new insights in the underlying mechanisms of anti-epidermal growth factor receptor therapeutic resistance in head and neck squamous cell carcinomas. Furthermore, these observations can form a solid basis for further in vivo and clinical studies on this topic, making advances in the treatment of head and neck squamous cell carcinomas.

(BELG J MED ONCOL 2015;9(2):74–6)

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Isolated lung perfusion as additional treatment for lung metastases

BJMO - volume 9, issue 1, february 2015

W. Den Hengst MD, J. Hendriks MD, PhD, F. Lardon PhD, P. Van Schil MD, PhD

The golden standard for the treatment of lung metastases remains complete surgical resection. Prognostic factors for patients with lung metastases are histology, number of metastases and disease-free interval. However, the chance of recurrent disease in the treated lung remains high after complete resection, even in combination with systemic chemotherapy. Systemic toxicity limits the dose of the latter, resulting in only limited local pulmonary control. Therefore, new techniques are developed to deliver a high-dose of chemotherapy selectively into the lung, reducing the risk of systemic toxicity. One of these techniques is isolated lung perfusion, which is comparable with isolated limb perfusion. This experimental surgical technique allows delivery of a very high-dose of chemotherapy with or without biological response modifiers to the lung, without the risk of systemic exposure. Experimental studies with this technique have shown its superiority in achieving higher tissue concentrations of chemotherapy in the target organ as well as improved survival in comparison with systemic chemotherapy. As shown in several phase I studies, this technique is technically feasible with minimal morbidity and minimal impact on pulmonary function. In a recent phase II study, an improved local pulmonary control was found in comparison with the literature. This review discusses the current status of isolated lung perfusion as well as newer, less invasive techniques to deliver high-dose chemotherapy selectively to the lung.

(BELG J MED ONCOL 2015;9(1):5–10)

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