A study on anti-tumor T lymphocytes opens up future therapeutic products for patients with acute myeloid leukemia
Publication date: 05-02-2024
Updated on: 05-02-2024
Estimated reading time: 1 min
A team of researchers from IRCCS Ospedale San Raffaele and Università Vita-Salute San Raffaele, led by Professor Chiara Bonini, Full Professor of UniSR Hematology and Group leader of the Unit of Experimental Immunology, demonstrated how anti-tumor T lymphocytes can be identified, monitored over time and characterized in patients with acute myeloid leukemia and how they can exploit inhibition mechanisms put in place by the tumor to escape recognition by our immune system.
The ultimate goal of the research project is to identify new reagents that could lead to the development of therapeutic products for patients with acute myeloid leukemia.
The study was recently published in the prestigious journal Science Advances.
Through detailed study of anti-tumor T lymphocytes in the peripheral blood of patients after hematopoietic stem cell transplantation, the researchers observed that these cells are present in 90 percent of the patients analyzed, but, unfortunately, despite this excellent premise, they are unable to perform their function as the “killer” in the immune system.
"The reason lies in the fact that these anti-tumor receptors are subject to “functional depletion,” caused by the presence on their surface of molecules that can “turn them off,” a phenomenon that seems to be particularly relevant for patients in whom disease recurrence occurs," says Francesco Manfredi, first author of the study,and a researcher at the Experimental Hematology Unit at the time of publication.
Dr. Eliana Ruggiero, a researcher at the same Unit and co-ultimate author of the study, adds: "By combining the detailed analysis of proteins expressed on anti-tumor T lymphocytes with transcriptome and peptidomain sequencing technologies (the latter activity, in collaboration with Professor Vincenzo Cerullo of the University of Helsinki), we have identified not only a library of TCRs, i.e., proteins expressed on the surface of T lymphocytes, capable of recognizing the tumor, but also molecules expressed by tumor cells that could be used as new therapeutic targets in the future."
Using “molecular scissors” made with CRISPR/Cas9 technology that can “cut” and delete specific genes of interest, the researchers then generated “armies” of tumor-specific T lymphocytes, inserting the identified anti-tumor TCRs into the cells.
Dr. Chiara Bonini points out, "The study opens up new hope for treatment of patients with acute myeloid leukemia. By exploiting the presence of anti-tumor T lymphocytes in almost all of the patients studied and the inability of these cells to recognize the tumor, we have been working to identify new reagents that can be used, in the future, to expand treatment options for patients with this disease."