Improving immunotherapy of cancer by patient-specific vaccines
The project aims to enhance specific immunotherapy to cancer for individual patients by adding adequate immunological help in DNA vaccines. LUMC will operate closely with consortium partner Immunetune B.V., a pioneering company developing genetic cancer vaccines. The design and production of DNA vaccines by the company will be analyzed in the LUMC for most optimal efficacy.
With over 15 million new patients per year, cancer is a leading worldwide health problem leading to severe societal impact for those affected and directly involved. The economic impact and burden of cancer is extremely high and increasing every year, WHO estimates for worldwide costs are 1.2 trillion dollar annually. There is still a high and unmet need for treatments attacking tumor tissue without the severe side effects of current treatments. Targeted immuno-oncology is a highly promising approach to combat and prevent recurrences of cancer. Following the success of immunotherapy with the so-called immune checkpoint blockers, showing tremendous improvement of therapy of e.g. melanoma and lung cancer but coincides with severe side effects, the innovation of this project is to develop more specific immunotherapy based on precisely designed therapeutic DNA vaccines.
Therapeutic vaccines have the advantage to direct our own immune system to the malignant cancer cells while leaving our healthy cells unharmed. This specific type of immune therapy can be expected to have very low side effects in contrast to classical therapies. The concept of our approach is to use the identified specific mutations present in cancer cells which makes these aggressive cells immunologically different from healthy body cells. These mutations will be included in our DNA vaccines to activate, expand specific immune cells to kill the tumor. Important is to optimally design such cancer vaccines. Crucial is to include strong immunological helper signals to properly activate the immune killer cells since most tumors actively suppress our immune system. The most optimal helper signals we have analyzed in this project. Using helped cancer-specific DNA vaccines we could show improved quality of the raised anti-cancer immune response and cures of mice with aggressive tumors.
Strikingly, the vaccine induced immune control of tumors was much more efficient using tumor-specific help than using than with universal help. This information is very important for the design of the most optimal specific immune therapy by DNA vaccination for individual cancer patients.
