A study on anti-tumor T lymphocytes opens up future therapeutic products against acute myeloid leukemia

A team of researchers from IRCCS Ospedale San Raffaele and Vita-Salute San Raffaele University, led by Prof. Chiara Bonini, Full professor of Hematology UniSR and Group leader of the Experimental Hematology Unit, has demonstrated how anti-tumor T lymphocytes can be identified, monitored over time and characterized in patients with acute myeloid leukemia and how the inhibitory mechanisms implemented by the tumor can be exploited to escape recognition by our immune system. The ultimate aim of the research project is to identify new reagents that could lead to the development of therapeutic products for patients suffering from acute myeloid leukemia. The study has been published in the prestigious journal Science Advances.

Through the detailed study of anti-tumor T lymphocytes in the peripheral blood of patients after hematopoietic stem cell transplantation, the researchers observed how these cells are present in 90% of the patients analyzed. Unfortunately, despite this excellent premise, they are unable to perform their function as "killers" of the immune system.

“The reason lies in the fact that these anti-tumor receptors are subject to “functional exhaustion”, caused by the presence on their surface of molecules capable of "switching them off," a phenomenon that seems to be particularly relevant for patients in whom disease recurrence occurs"

states Francesco Manfredi, first author of the study, former researcher at the Experimental Hematology Unit.

Dr. Eliana Ruggiero, researcher at the same Unit and co-last author of the study, adds:

“By combining the detailed analysis of the proteins expressed on anti-tumor T lymphocytes with transcriptome and peptidome 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. the proteins expressed on the surface of T lymphocytes, capable of recognizing the tumor, but also a library of molecules expressed by tumor cells which could in the future be used as a new therapeutic target".

Using "molecular scissors", created with CRISPR/Cas9 technology, capable of "cutting" and eliminating specific genes of interest, the researchers then generated "armies" of tumor-specific T lymphocytes, inserting the identified anti-tumor TCRs into the cells.

Prof. Bonini concludes:

“The study opens up new hopes for a cure for patients suffering from 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 worked to identify new reagents that can be used, in the future, to broaden the therapeutic options of patients suffering from this pathology."