Cancer immunotherapy as a strategy to treat cancer
The understanding of the biological and molecular mechanisms behind cancer has substantially improved over the past 20 years. However, treatment outcome of cancer has not always followed suit. Conventional treatment strategies (surgery, chemo- and radiotherapy) are in many cases not able to eradicate all tumor cells present in the body, either in the primary tumor or in metastases. In addition, tumor cells often become resistant to certain forms of chemotherapy. Together, this causes many cancer patients to relapse after initial treatment, and this reduces the overall survival rate. Thus, unmet needs remain for strategies that guarantee removal of all remaining tumor cells.
Immunotherapy is an increasingly accepted approach that has the potential to reduce tumor mass and eradicate remaining tumor cells throughout the body. This ultimately leads to prolonged overall survival. Immunotherapy is based on the principle of using the body's own immune system to find and destroy tumor cells. It is more and more used as a second line therapy, following conventional first line treatments. A big advantage of immunotherapy is that it targets different molecular pathways than chemo- and radiotherapy, allowing also for eradication of resistant tumor cells.
Cancer vaccines aim to stimulate the immune system to attack cancer cells by delivering tumor associated antigens (TAA) to the immune system. Cancer vaccines act by delivering such TAA to dendritic cells (DC), and this eventually results in a T-cell mediated-attack of the tumor. Patient-derived DC themselves are often used for ex vivo loading of TAA and preparation of an anti-cancer vaccine.
Development DCOne® derived products
DCPrime's core technology is based on the proprietary DCOne® platform, derived from a precursor human dendritic cell line and designed to deliver TAA. All other currently available DC-based cancer vaccines use dendritic cells derived from patients. Isolation of these cells involves a laborious and expensive procedure, hampered by donor variability and thus quality control, and sometimes by limited availability of DC precursors. As such, these patient-derived DC-based vaccines are not suitable for scalable production. The DCOne® platform is developed to circumvent these obstacles and allows for generation of off-the-shelf DC vaccines, ensuring a robust supply of DCs and vaccines of consistent quality.
The figure below outlines the process for production of DCOne®-derived DC vaccines. DCOne® cells (a) behave as the immortalized equivalents of DC precursor cells prepared from blood. Upon stimulation through a proprietary process (b), these proliferating precursor DC differentiate (c) and mature (d) into fully functional DC (e) that are able to induce specific T-cell and antibody responses that subsequently kill tumor cells. The DCOne® cell line is originally derived from a patient with acute myeloid leukemia (AML) and expresses multiple AML-specific antigens. This makes the DCOne® platform particularly suitable for treatment of AML patients, which therefore became the first patient population in which to test DCOne®-derived product DCP-001.
A unique selling point of the DCOne®platform is that in addition to being applicable to treatment of AML, it can be applied to a much broader range of cancer types. DCPrime has shown pre-clinically that DCOne® cells can be antigen-loaded with mRNA, proteins and peptides, and various viral vectors. Such antigen-loaded DCOne® cells can be used alone, or in fixed ratios and in different combinations. Together, this allows for production of any vaccine targeting any tumor in a specific individual, making the platform broadly applicable, and ensuring a highly targeted approach to cancer treatment.
Last updated: augustus 16, 2016