Project: Development of a large-scale production process for dendritic cell vaccines for the treatment of cancer

In this project, DCPrime BV and EUFETS GmbH unite forces to develop the first technology platform in the world for commercial-scale production of standardised dendritic cell based cancer vaccines. _x000D__x000D_Cancer is still the number one killer disease in the human population and its prevalence will continue to increase with the aging population. There is an immense unmet medical and industrial need to identify effective means for cancer management in addition to other therapies, such as targeted and chemotherapy. While in many cases cancer cannot be cured, approaches that are less toxic and more durable than chemotherapy and targeted therapies are gaining interest. Cancer vaccines are amongst the most promising as responses that are triggered by these vaccines reduce the chances for recurrences that inevitably occur in many cancer types. With cancer vaccines, the immune system is stimulated to destroy tumour cells by presentation of tumour-specific antigens to immune effector cells (ref 1). This can be achieved by the direct vaccination of cancer-antigens to the patient or through infusion of patient-based (autologous) or donor-derived (allogeneic) dendritic cells (DCs) that carry the antigens (ref 2,3,4). DCs are uniquely able to initiate primary immune responses and represent the most potent antigen presenting cells. Importantly, DC vaccines have shown in clinical studies to be safe and well-tolerated, and they do induce antigen-specific CD4+ and CD8+ effector T cells responses, plus antibody responses, which is exactly the desired effect (ref 2). DC vaccines are thus regarded to have great promise for the treatment of cancer. _x000D__x000D_Novel approaches for DC vaccines are urgently needed, since conventional autologous DCs suffer from patient-to-patient variability, resulting in highly inconsistent clinical results and their use is laborious, time-consuming and expensive which obstructs large industrial interest. A highly-exiting approach is the use of allogeneic DC vaccines that potentially induce a much more potent immune response, and could be generated from cell lines. In addition, such lines would offer a standardised, off-the-shelf product, which is much more attractive from clinical and commercial perspective. Despite this advantageous profile, off-the-shelf DC vaccines based on cell lines have proven difficult to be generated under large-scale conditions and no organisation to date has been able to bring such vaccines to clinical trials of sufficient statistical power. This situation is about to change by the fusion of state-of-the-art technologies and expertise of DCPrime and EUFETS. These companies put forward a high-potential off-the-shelf DC vaccine, and Europe's best infrastructure for commercial-scale production of such vaccines. _x000D__x000D_DCPrime’s platform (DCOne) combines the power of the currently used autologous DC vaccines with the advantages of allogeneic stimulation of the immune system, and the simple logistics of off-the-shelf products. In addition to DCOne that endogenously expresses multiple tumor antigens (referred to as unloaded), DCPrime is developing strategies to load DCOne with peptides from multiple antigens. Dependent on which cancer antigens are loaded onto DCOne, different cancer indications can be treated. With this technology platform (Addendum figure 1), there is a unique opportunity to address unmet needs in cancer by the commercialisation of standardised, off-the-shelf DC vaccines._x000D__x000D_The first clinical results are encouraging. A phase I/IIa dose-escalation study (started mid 2011) is being performed in AML patients for which currently no treatment is available anymore and are at high risk of relapse (within months to a year). The data show that the vaccine is well-tolerated, does not induce product-related safety or toxicity issues, and the vaccine induces both T and B cell responses. This demonstrates that the vaccine is capable of generating the integrated and diverse immune responses that are known to be the most effective for getting anti-tumor responses. _x000D__x000D_These exiting results provide the rationale for the preparation of vaccine batches for clinical phase II studies and beyond, and also start clinical phase I/IIa studies in other cancer indications. The execution of clinical phase II studies requires large batches of DCOne cells that are cultured under GMP conditions. These batches will provide the material volume needed to treat patients in the clinical study setting and will create the potential to produce the vaccines in quantities needed after product approval. One hurdle, however, is that currently there is no process for the large-scale development of DCs. _x000D__x000D_Recognising the unmet needs described above and anticipating the commercial opportunities, the CO objective in DC-VACCS is to develop a GMP-grade commercial-scale production process for allogeneic antigen-loaded and 'unloaded' DCOne as a vaccine for the treatment of AML as well as other cancer indications._x000D_

Acronym DC-VACCS (Reference Number: 7940)
Duration 01/04/2013 - 30/06/2016
Project Topic DCPrime BV and EUFETS GmbH unite forces to develop the first technology platform in the world for commercial-scale production of standardised dendritic cell based cancer vaccines. This enables further clinical investigation and future marketing of this high-potential cancer therapy.
Network Eurostars
Call Eurostars Cut-Off 9

Project partner

Number Name Role Country
2 DCPrime BV Coordinator Netherlands
2 EUFETS GmbH Partner Germany