Immunotherapy

Recent studies have shown that supporting the natural anti-tumor activity of the immune system using a new generation of drugs (immune checkpoint inhibitors, ICI) can be an extremely effective weapon in the fight against cancer. However, the efficacy of these treatments varies depending on the type of tumor. There are in fact tumors that present a tumor microenvironment containing substantial numbers of immune cells. These are the so-called “immunological warm” tumors that respond better to immunological therapies. In contrast, tumors showing little lymphocyte infiltrate in the microenvironment are “immunologically cold”. These tumors are generally less susceptible to the therapy with ICIs.

The aim of our projects is to transform “cold” tumors, such as colorectal cancers (CRC), into immunologically “warm” tumors and making them therefore more susceptible for the treatment with ICIs. We follow two main strategies to achieve this goal:

• the creation of new tumor targeting BiTEs (bispecific T cell engagers), able to simultaneously bind a specific tumor antigen and a receptor on T lymphocytes and, consequently, directing their cytotoxic activity against tumor cells.
• the production of an innovative fourth generation chimeric antigen receptor T-cell able to directly eliminate the tumor cells, but also to subsequently release ligands able to stimulate receptors important for the activation of antigen presenting cells of the innate immune system. We hypothesise that this will help the body to initiate a general anti-tumor response involving endogenous immune cells of the body. (PI: T.L. Haas)