Research
1. Identification and characterization of anti-regulatory T cells
During the last decade, we have described the existence of circulating effector T cells, referred to as "anti-regulatory T cells" (anti-Tregs), that specifically target normal self-proteins, such as IDO, PD-L1, Arginase, and TGFβ, which are tumor microenvironment antigens (TMAs). Anti-Tregs may directly attack tumor cells but can also modulate the tumor microenvironment, rendering it immunocompetent and hostile to tumors. We are identifying novel TMAs and characterizing their ability to target and modulate regulatory cells and cancer cells.
2. Immune modulatory vaccines
We are examining the anti-cancer effects of immune modulatory vaccines (IMVs) in pre-clinical models as well as in investigator-initiated clinical trials. We are characterizing the immune modulatory effects in the microenvironment, the phenotype of the induced immune responses, and the safety of different vaccines. Furthermore, we are exploring how to incorporate different TMAs into the vaccines and the optimal combinations with other therapeutic modalities, including immune checkpoint inhibitors and cancer vaccines.
3. Shared neoantigens in solid and hematological cancers
We have made significant discoveries regarding the immunogenic potential of neo-antigens in chronic blood cancers, specifically chronic myeloproliferative neoplasms (MPN). These findings demonstrated that cells carrying the most frequently occurring mutations in MPN are targeted and eliminated by the immune system, resulting in the initiation of two clinical trials. Additionally, we are investigating the frequency and phenotype of shared neoepitopes in solid cancers and healthy donors, which exhibit robust immune responses to tumor-specific mutations.
New Project: Targeting the tumor microenvironment with CRISPR-engineered T cells through T cell receptor replacement.
CCIT-dk excels in adaptive cell therapy (ACT) and immune modulatory vaccination (IMV) for combating cancer. Our latest project aims to integrate these treatment strategies by developing genetically modified T cells for ACT, targeting antigens utilized in IMV. The objective is to assess whether this approach, termed aACT, can induce comparable or enhanced modulation of the tumor microenvironment (TME). We plan to genetically engineer primary T cells to express the specific T cell receptors (TCRs) present on anti-Tregs, thereby initiating a tumor-specific immune response.