Department of Cell Therapy
Cancer immunotherapy has gained a lot of interest over the last few years due to the success of immune checkpoint inhibitors in treating cancer. These inhibitors have been shown to increase survival of patients with advanced cancers. The immune checkpoint inhibitors prevent cancer-induced immune suppression and thereby restore the function of T cells that are programmed and trained to fight against tumor cells. However, abrogating immune suppression is not always sufficient, as anti-tumor T cell immunity might be severely hampered or even absent in cancer patients. Therefore, there is an urgent need for novel cancer therapies that induce anti-tumor responses in patients to enhance the effect of immune checkpoint inhibitors.
Dendritic cells (DCs) as professional antigen presenting cells are vital for the activation of immune responses and therefore DC-based cancer immunotherapy can be a very powerful method to induce anti-tumor immune responses in patients. This immunotherapy is based on training autologous DCs from patients to induce anti-tumor immunity. Several studies have shown that DC-based immunotherapy is safe and can improve survival of cancer patients by eliciting anti-tumor immunity. Although proof-of-principle has been provided for DC-based cancer immunotherapy, the clinical success has been suboptimal. For DC-based immunotherapy it is crucial to develop better methods to train, program and activate DCs to induce powerful anti-tumor immunity, which depends on robust activation of T helper cells to propagate anti-tumor immunity as well as cytotoxic T cells for killing tumor cells. This is the decisive step in the induction of anti-tumor immunity, since DCs can be activated by different stimuli, leading to very distinct immune responses. In particular, it has become clear that DC activation program can be tailored to the pathogen or tumor by triggering a specific combination of receptors, such as Toll-like receptors, C-type lectin receptors, and cytokine receptors. Our knowledge about these receptors and the functional consequences of different DC maturation steps provides us with powerful tools to develop novel DC activation methods that lead to effective anti-tumor immunity.
Considering the unique technical skills, expertise and clinical facilities in the Department of Experimental Immunology (EXIM), Academic Medical Center, University of Amsterdam, we have planned a comprehensive program in which through a long lasting collaboration and performing several joint projects, DC immunotherapy for treatment of different cancers will be set up, developed and run in our department.
Our group is experts in DC biology and immune signaling by pattern recognition receptors such as Toll-like receptors and C-type lectin receptors. Our Dutch collaborators belong to the world-leaders in understanding the function of DC and in inducing specific T cell responses paramount to antitumor immunity (Gringhuis et al. Nature Immunol 2009a,b, 2010 and 2012; Nat Comm 2014a,b; Mesman et al. Cell Host & Microbes; Wevers et al. Cell Host & Microbes). We have identified different signaling pathways in DC that allow us to program DC to shape adaptive immunity specifically against cancer to induce strong T helper 1 responses and cytotoxic T cells.
We have identified specific stimuli and receptors that will allow development of dendritic cell-based vaccines that tremendously enhance the effectivity of anti-tumor responses. We not only study the antigen uptake pathway but we also design novel adjuvants to induce the most efficient anti-tumor responses in patients.
Together with clinicians from Breast Cancer Research Center, we use our expertise to develop DC-based immunotherapy program in Iran. This program consists of fundamental and pre-clinical research combined with clinical trials to successfully treat cancer patients.
In this program we develop and implement an innovative DC cancer immunotherapy for treating cancer patients. We will initially focus on breast and/or prostate cancer but we will also develop the DC immunotherapy for other cancers such as leukemia, and colon cancer. Once the DC immunotherapy has been developed for one cancer, it can be adapted for other cancers since the basic method of ex vivo DC generation and activation remains the same.