Cancer Immunotherapy

Cancer is characterized by unregulated and uncontrolled cell growth leading to the formation of malignant tumors that can invade other parts of the body (metastasis) and impair the normal function(s) of the affected organ(s).

Cancer immunotherapy intends to mobilize a patient’s immune system to fight the disease. This approach was chosen as the “Breakthrough of the year 2013” by SCIENCE magazine.

Cancer immunotherapy can be divided into passive immunotherapy, i.e. transfer of certain immune effector cells (T-cells) or antibodies, or active immunotherapy through therapeutic vaccination. Therapeutic cancer vaccines target antigens that are selectively expressed or overexpressed by cancer cells compared to healthy cells.

Active Cancer Immunotherapy

CureVac's approach of mRNA-based cancer immunotherapy is among a class of active immunotherapies designed to trigger the patient’s immune system to attack cancer cells.

Dendritic cells (DCs) and other antigen presenting cells (APCs) are critical for initiating effective immune responses. The first step is the capture and presentation of tumor-associated antigens by APCs. The tumor-associated antigens can be delivered by vaccination. Then, APCs express and/or process the captured antigen for its presentation or cross-presentation on major histocompatibility complex (MHC) molecules and migrate to the lymph nodes. Importantly, the capture and presentation must occur in the presence of an immunogenic maturation stimulus, e.g. via Toll-like receptors (TLR), in order to stimulate both humoral (antibody-mediated) responses and cellular (antigen-specific T-cell) responses.

RNActive® Cancer Immunotherapy

CureVac’s products typically consist of several mRNA molecules that encode for specific tumor-associated antigens.

Before the antigen-presenting cells (APCs) can present a tumor-specific antigen (TSA) or tumor-associated antigen (TAA) to the T-cells, they must take up the RNActive® immunotherapy and express the corresponding antigens in the appropriate way. They then present the antigen to CD4+ helper T-cells and CD8+ cytotoxic T-cells. CD4+ helper T-cells can only be activated in a tumor-specific way if the tumor antigen is presented on a MHC class II molecule, whereas CD8+ cytotoxic T-cells require an antigen presented on a MHC class I molecule. APCs as dendritic cells have the unique capacity to present tumor antigens to CD4+ helper T-cells and CD8+ cytotoxic T-cells.

RNActive® immunotherapies support both antigen expression and immune stimulation, mediated by Toll-like receptor 7 (TLR7).