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Project

Translational research on the novel combination of chemotherapy and anti-CD70 immunotherapy to improve treatment outcome in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) retains its position as the most lethal type of cancer with around 1.3 million deaths per year worldwide and a marginally improving 5-year overall survival rate which remains below 20%, pointing to the need for new therapeutic options. Immunotherapy, in which the patient's immune system is used to selectively eliminate cancer cells, is considered a very promising candidate. Results of the recently approved immunotherapeutic agent nivolumab underscore the potential of immunotherapy in NSCLC, but also leave room for improvement. This study will focus on the CD70-CD27 signaling pathway as an interesting novel target to enhance anti-tumoral immune responses in NSCLC in combination with low doses of chemotherapy. CD70 is a member of the tumor necrosis factor family and its expression is normally restricted to activated T and B cells. Constitutive expression of CD70 by tumor cells can facilitate immune evasion by increasing the amount of suppressive regulatory T cells, inducing T cell apoptosis and skewing T cells towards T cell exhaustion. Previously, we have detected constitutive overexpression of CD70 in NSCLC tumor specimens, also in patients that lack other targeted treatment options. This CD70 expression can be exploited by CD70-targeting antibody-dependent cellular cytotoxicity (ADCC)-inducing antibodies. Our preliminary data show that the combination of anti-CD70 therapy with low doses of chemotherapy significantly increases cytotoxicity of the drug, compared to single treatment regimens. The main objective of the current project proposal is to rationally design and to preclinically evaluate a combination therapy of chemotherapy with CD70-targeted immunotherapy as a novel treatment option for patients with NSCLC.
Date:1 Oct 2016 →  31 Mar 2022
Keywords:CHEMOTHERAPY, IMMUNOTHERAPY, LUNG CANCER
Disciplines:Cancer therapy, Immunomodulation therapy