Stimulating a memory T cell response
Many attempts have been made to develop a cancer vaccine based on tumour-derived antigens (typically proteins or peptides) that are expressed on cancer cells but not on the healthy cells. However, the majority of clinical trials have failed to induce a durable vaccine-related response in patients. The general idea behind a cancer vaccine is to feed the dendritic cells (DCs) of the immune system with tumour-derived antigens. DCs subsequently present the antigens to the cytotoxic T cells, which are the killer cells of the immune system. This interaction activates the T cells and they can subsequently recognise and kill cancer cells that express the specific antigen that was presented to them. Most importantly, the T cells can be stimulated not just to kill cancer cells but also to remember what the cancer cells look like in case some of them survive the treatment and come back to form a second tumour. This is a desirable effect when designing a cancer vaccine because the induction of a memory T cell response means that the patient has been vaccinated against a relapse of his or her cancer.
A liposome-based cancer vaccine
DCs are extremely important players in the induction of a T cell mediated anti-tumour immune response. Using the novel technology developed in the CBIO group at DTU Nanotech, it is possible to target DCs with a combination of tumour antigens and a so-called “danger signal” in the form of an immunostimulatory compound that activates the DC. The antigen and the immunostimulatory compound are co-formulated in a nanoparticle with a lipid bilayer – a liposome. This specific liposome formulation has a long circulation time when injected into mice. This means that the liposomes accumulate in the tumour and spleen and this ensures a high uptake by the present DCs. When the liposomes are absorbed by the DCs, the antigens are released inside the cell, processed and presented to the antigen specific cytotoxic T cells. Most importantly, the co-delivery of the antigen and an immunostimulatory compound ensures a proper activation of the DC, which results in an improved T cell activation and ultimately a more efficient anti-tumour response. By combining the delivery of tumour-derived antigens and an immunostimulatory compound in one single liposome to the DCs, this technology tackles some of the difficulties in cancer vaccine development such as an insufficient delivery of antigen and lack of proper DC activation.
The ability of the liposomes to work as efficient antigen-delivery entities is being evaluated using in vitro assays with DCs that have been isolated from mice. Mie Hübbe is one of the PhD students working on these experiments. She states, “we are currently evaluating the antigen-presentation induced by treatment of DCs with our liposomes. So far, the results look very promising. We detect a high presentation when the antigens are delivered with our liposomes and most importantly, the DCs are able to induce T cell activation and proliferation in vitro.”
Based on these promising results, the next step for Mie and her fellow researchers is to test the liposomes in tumour-bearing mice where the effect of the treatment will be evaluated by measuring the growth of the tumours compared to a control group. The hope is that a treatment with the liposomes will slow down the growth of the tumour or even cure the mice completely.
Mie Hübbe concludes, “our technology allows us to conjugate virtually any tumour antigen to our liposomes. This makes our platform unique and widely applicable, as it can be used to deliver combinations of tumour antigens, which deals with the heterogeneity of cancer cells in a tumour. In the future, our technology may be used to deliver a specific combination of tumour antigens that have been selected based on sequencing of tumour samples from patients. This is an important step towards the tailored design of a cancer vaccine that fits the individual patient.”
Source : Technical University of Denmark