DC4U’s GlycoDCTM dendritic cell targeting technology can be applied to significantly enhance anti-tumor immunity and generate a long-lasting anti-tumor response. This can be achieved by glycan modifications of tumor associated antigens or peptides derived from these antigens.
Successful immunotherapy against cancer depends on the activation of tumor-specific CD8+T cells as these cells have the appropriate machinery to destroy cancer cells. In addition, activation of CD4+T cells has shown to be beneficial to obtain potent tumor-specific CD8+T cells. The efficacy of T cell activation critically depends on how the antigen is processed by antigen presenting cells (APCs) such as dendritic cells (DCs) and routed intracellular to be presented on MHC molecules. T cells recognize tumor antigen-MHC complexes with their T-cell receptors (TCRs) as well as signals derived after engagement of co-stimulatory receptors on APCs. DCs are the most potent APCs to activate T-cells and are present as network in peripheral tissues such as skin and mucosal areas. Thus, strategies aim to optimally gear DCs for this important task. The main challenge is to efficiently target and trigger DCs to elicit a strong, specific and long lasting immune response, without causing adverse effects.
Our technology is based on the discovery of prof. Yvette van Kooyk that C-type lectin receptors expressed on DCs have a high binding specificity for specific glycan structures. Glycan modification of tumor antigen-derived peptides enables specific targeting of the formulation to DCs, as well as optimal intracellular routing for MHC loading. DCs will subsequently induce tumor antigen specific CD4+T cells, and long lasting CD8+T cell responses. An effector T cell mediated tumor attack results and the tumor cells will be killed.
Glycans can be linked to any type of tumor antigen or vehicle that contains the tumor antigen(s). Our GlycoDCTM technology will be validated for melanoma as a first application area, using melanoma specific antigens. This will offer a completely new and effective targeting platform for other cancers, including colorectal cancer, ovarian cancer, non-small-cell lung cancer (NSCLC), brain cancer, renal cancer, bladder cancer, head and neck squamous cell carcinoma, prostate cancer and breast cancer. For all of these indications, tumor antigen based therapeutics currently fill the drug pipeline, all representing opportunities for improvement by our GlycoDCTM technology. To exploit this potential, we offer business and partnering options to pharmaceutical companies actively involved in cancer immunotherapy.
