A nano-sized message: liposome-based vaccines for anti-tumor immunity

The last decades were marked by impressive developments in the field of tumor immunology. Therapies aimed to harness the immune system in the fight against cancer have become clinically relevant next to surgery, radio- and chemotherapy. In order to appreciate the functions of the immune system in the context of cancer we should dive into the nature of cancer and the components that make up the immune system. To start, the immune system encompasses a complex system of cells, proteins and other molecules aimed to protect the body from invading pathogens. Immune cells can broadly be divided in the innate and adaptive immune system. Cells that belong to the innate immune system react quickly to infections and examples of these cells are macrophages and dendritic cells. These cells are known for their ability to take up foreign material or dead cells and are also able to present part of these materials (called antigens) to cells of the adaptive immune system (T- and B-cells). Subsequently, these cells can kill virus infected cells or produce antibodies, respectively. T- and B-cells respond later in time, but in contrast to cells of the innate immune system, in a highly specific (antigen-specific) manner. If we zoom in on the structure and components of, for example, bacteria and viruses, it will not be surprising that they can be seen as foreign to the body. In contrast to these pathogens, tumor cells are originally not foreign and can be considered as ‘self’. However, tumor cells have acquired mutations and as a consequence can express proteins that are normally not expressed or expressed in low amounts (collectively referred to as tumor antigens). Due to the accumulation of these antigens, the immune system can recognize tumors as foreign and therefore eliminate them. Spontaneous immune responses against tumors are insufficient to control tumor growth in the event of clinical manifestation. To boost the immune system, vaccinations can be given to aid responses against tumors. Similar to vaccinations against pathogens, the immune system ‘learns’ to respond to vaccine incorporated tumor antigen. One relatively well-known functional response to vaccines is the production of antibodies (by B cells), but infected or mutated (tumor) cells can also be eliminated (by cytotoxic (cell-killing) T cells). In the case of tumor vaccinations, the focus is on the generation of antigen-specific T cells, which can recognize and eliminate mutated tumor cells. Vaccination can therefore boost the number of tumor-specific T cells, which then leads to an anti-tumor response. In order to develop a tumor vaccine, we can identify three important components. First of all, tumor antigen, since T cells respond in a highly specific manner. So, vaccine incorporated tumor antigen must overlap with the antigens found in the mutated tumor. In addition, vaccine adjuvant is important as the adjuvant is an immune-stimulating molecule that causes inflammation and thus ensures that the immune system actually responds to the vaccine antigen. If vaccine antigen is not presented in the context of inflammation, the immune system does not respond, insufficiently or in an incorrect manner. The third component of vaccinations are (targeted) vaccine carriers. In our research we have used liposomes (small lipid-based enclosed structures) in which we can incorporate vaccine antigen and adjuvant. We can decorate liposomes with certain sugars in order to reach cells that express receptors that recognize these specific sugar structures.