Medigene’s new generation of dendritic cell (DC) vaccines have optimal immunotherapeutic potential to activate potent anti-tumor immune responses
Medigene has established a DC vaccine platform for the generation of antigen-tailored DC vaccines prepared from patients’ own blood cells.
Medigene’s has developed new, fast, and efficient methods for generating autologous (patient-derived) mature DCs with the ability to activate patients’ lymphocytes (both T cells and natural killer cells). For a given type of tumor, several antigens are introduced into mature patient-derived DCs, which are subsequently applied as vaccines. With this modular antigen approach Medigene can develop vaccines for a wide variety of different tumor types.
The DC vaccines can interact with T cells and induce antigen-specific T cells to proliferate and gain functions that allow them to attack tumor cells. Vaccine-activated T cells can thereby specifically recognize and eliminate antigen-expressing tumor cells. They can also induce natural killer cells to become active and attack tumor cells. The Medigene approach also allows DC vaccines to be developed using neoantigens identified in the tumors of individual patients.
Presently, DC vaccines have worked best in patients with low numbers of tumor cells, such as the minimal residual disease that is often left after surgery, radiation, or chemotherapy. The advantageous safety profile of DC vaccines in general, as observed in numerous clinical trials in the past, is not detrimental to the patients’ quality of life during DC vaccine immunotherapy.
Medigene’s DC vaccine platform offers unique advantages:
- Young and potent DCs can be manufactured in just three days.
- High quantity yields of DC vaccines for up to two years or longer.
- Cells stored frozen and administered through simple injections under the skin.
- Collection of antigens as off-the-shelf reagents to tailor DC vaccines according to medical need.
Medigene holds a patent in the US, Australia and Europe for the manufacturing of mature dendritic cells. The patent protects our process to generate polarized mature dendritic cells using our unique maturation cocktail.
Specific characteristics of Medigene’s new generation DC vaccines:
- Medigene’s DCs display a surface profile composed of high levels of molecules needed for co-stimulation of T cells, leading to optimal activation.
- DCs manufactured following Medigene’s protocol produce bioactive IL-12, a critical cytokine that is needed for effective activation of anti-tumor immunity.
- Medigene’s DCs can also activate natural killer cells of the innate immune system to provide immune synergy of the innate and adaptive immune systems.
Personalized cancer treatment with DC vaccines
Profile and function of dendritic cells
In 1973, Prof. Dr. Zanvil Cohn and Prof. Dr. Ralph Steinman discovered the DC, a new immune cell that plays a crucial role in bridging innate and adaptive immunity, and further characterized it over the next several decades. Prof. Dr. Steinman was awarded with the Nobel Prize in Physiology or Medicine in 2011 for his pioneer work on the discovery of DCs. They are the most potent antigen-presenting cells that hold the task in our body to take up, process and present peptide fragments of on their cell surface in conjunction with MHC molecules. This display of MHC-peptide complexes on DCs leads to activation of either CD4+ or CD8+ T cells, dependent upon the display of the peptide fragments by MHC class II or MHC class I molecules respectively.
Medigene’s new generation DC vaccines deliver three signals to T cells to activate optimal responses. First, controlled expression of MHC-peptide ligands is achieved using RNA as the source of antigen that is processed into appropriate fragments that are presented by MHC class I and class II molecules of the DC. The surface display of MHC-peptide ligands allows T cells to bind to the DCs via their TCRs and this interaction delivers an activation signal to the T cells. The second signal contributes to the survival of the T cells. At day three, mature DCs display a strong positive co-stimulatory profile through high expression of several stimulatory molecules of the B7 family, among others. The third signal delivered by the DCs to the T cells is provided by secreted bioactive IL-12 that binds to the IL-12 receptors on the T cells and contributes to their differentiation into potent effector cells.
Medigene’s dendritic cell vaccines deliver three signals to activate optimal anti-tumor immune responses