The ability of the immune system to eliminate tumor cells has been proven and well documented over the last two decades. Tumor cells can be eliminated by cytotoxic T cells that recognize tumor antigens, most of which represent mutations that have occurred over time during metaplastic transformation of a normal cell to a malignant cell.
Currently there are several types of immunotherapies in development and in clinical use that either target cancer-mediated immune escape mechanism or boost the immune system. These include agonist for dendritic cell activation, cancer vaccines, T-cell therapy and immune checkpoint inhibitors.
New immunotherapies, such as immune checkpoint inhibitors, tend to be most effective on tumors that are T-cell inflamed (hot), whereas those that are not T-cell inflamed (cold) are much less responsive to immunotherapy.
New immunotherapeutic strategies are therefore needed to enhance the presence of T cells in cold tumor and thereby making them more sensitive to immunotherapy.
New treatment strategies and challenges
An effective T-cell mediated immune response can only occur if antigens are released from tumor cells and taken up by dendritic cells. The dendritic cells present the antigens to T cells, which then become activated and migrate into circulation to attack cancer cells.
Tumor heterogeneity describes the observation that different tumor cells can display distinct genetical and phenotypical profiles, including mutational burden. Heterogeneity of tumor cells introduces significant challenges when it comes to choice of treatment strategies because tumor cells may exhibit different sensitivity to conventional therapy (i.e. chemotherapy and radiation).
Agents that can effectively release tumor antigens from all tumor cell phenotypes are critical to generate an effective T-cell response that will target all phenotypes present in a treated tumor.
Lytix Biopharma has developed an oncolytic peptide, LTX-315, that, when given intra-tumorally generates an immune response against a broad antigen repertoire without the need for identification of the antigens. Therefore, local use of LTX-315 has the potential to make cold tumors with low mutational burden hot and T-cell inflamed. LTX-315 can induce complete regression both in experimental models and in cancer patients through an oncolytic mode of action, resulting in the release of tumor antigens from all tumor cell phenotypes invoking a polyclonal T-cell response. LTX-315`s ability to activate and prime a broad repertoire of T-cell clones makes it ideal for combining with other local and systemic immunotherapies.