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A new therapy to reactivate the immune system of patients with blood cancers

A new therapeutic strategy to reactivate the immune response in patients suffering from myelofibrosis, a blood neoplasm, has been developed by a group of researchers at the Interdepartmental Centre for Stem Cells and Regenerative Medicine (CIDSTEM) of Unimore . The research was coordinated by Professor Rossella Manfredini of the university's Department of Metabolic Biomedical Sciences and Neuroscience. The results of the study, supported by the AIRC Foundation, emerged as part of the '5 per mille' MYNERVA programme coordinated by Professor Alessandro Vannucchi. The data were published in the American Journal of Hematology', a leading international haematology journal of the Wiley Group.

Myelofibrosis is the most severe form of the Philadelphia-negative chronic myeloproliferative neoplasms. Despite the introduction of ruxolitinib, a targeted drug for the treatment of patients, to date the only effective therapy is bone marrow transplantation, which, however, presents a high risk of relapse and death in these patients.

The results obtained by Prof. Manfredini's group (Dr. Ruggiero Norfo, Dr. Lara Tavernari, Dr. Sebastiano Rontauroli) showed that cytotoxic T lymphocytes, cells of the immune system that are normally able to kill tumour cells, lose this ability in patients with myelofibrosis. The function can however be reactivated, in exhausted T lymphocytes, by a drug already in use in clinical practice for other tumours, but never evaluated in these patients.

 “The targeted therapies currently available for the treatment of patients with myelofibrosis are not able to effectively counteract the expansion of cancer cells,” says Prof. Manfredini. "The identification of new therapeutic strategies is of crucial importance to overcome these limitations and provide physicians with a new tool for treating patients. For this study, we focused on a drug that is already used in clinical practice in other cancers to accelerate the transfer of results from the laboratory bench to the patient's bedside.”

“Our results showed that cytotoxic T-lymphocytes from myelofibrosis patients, compared to healthy controls, have higher levels of CTLA-4, an 'immune checkpoint', i.e. a molecular switch that is normally used to prevent an excessive T-lymphocyte response and is instead exploited by tumour cells to evade immune surveillance,' explains Dr Lara Tavernari . "Based on these data, we focused on the effect of inhibiting this immunosuppressive axis.”

“In laboratorio abbiamo sviluppato un sistema per studiare l’interazione fra linfociti T e cellule tumorali” spiega il Dottor Sebastiano RontauroliAbbiamo così scoperto che l'attivazione dei linfociti T citotossici dei pazienti con mielofibrosi è inibita dalla presenza di cellule tumorali, ma può essere ristabilita attraverso l’impiego di un anticorpo monoclonale anti-CTLA-4.”

“Abbiamo quindi effettuato in animali di laboratorio il trapianto di cellule di pazienti” aggiunge il Dottor Ruggiero Norfo . “ed osservato che l'inibizione di CTLA-4 con anticorpi monoclonali è in grado di riattivare i linfociti T citotossici dei pazienti, promuovendo l'eliminazione delle cellule tumorali, incluse le cellule staminali tumorali, responsabili del mantenimento della malattia”.

'Overall,' Professor Manfredini concludes, 'these data show that the reactivation of exhausted cytotoxic T lymphocytes may represent an effective new therapeutic target for the treatment of myelofibrosis patients. This could potentially be useful for the development of more targeted and precise treatments. Since the drug we use is well tolerated in patients with other types of tumours, we are planning to develop a clinical trial to start as soon as the necessary approvals are obtained."

"This result of great scientific relevance and considerable application potential, achieved by Prof. Manfredini's group," concludes Professor Michele Zoli, Director of the Department of Metabolic Biomedical Sciences and Neuroscience, "confirms the great scientific value of the Department's research groups and is the best recognition of the departmental policy for the development of translational research."


Rossella Manfredini

Graduated in 1988 in Biological Sciences at the University of Modena with a grade of 110/110 and summa cum laude, in 1994 she obtained a Doctorate in Experimental Haematology and in 1996 a Specialisation in Biochemistry and Clinical Chemistry. Awarded AIRC and Lega Italiana Lotta contro i Tumori scholarships, she was a post doc at Temple University in Philadelphia (USA), obtaining in 1998 the US patent for "Use of AS c-fes and ATRA oligonucleotides in M3 type leukaemias". Since 2013 she has been Full Professor of Applied Biology at Unimore. She is author of 117 scientific publications in international high impact journals. She has been working for more than thirty years on the biology of stem cells, both normal and pathological, with particular reference to the molecular mechanisms underlying the processes of self-renewal, proliferation and differentiation. His main research topics are: molecular and functional characterisation of normal and leukaemic haemopoietic stem cells, study of the clonal heterogeneity of the leukaemic stem compartment and study of the functional depletion of cytotoxic T lymphocytes in myeloproliferative neoplasms.


Pictured from left: Dr. Ruggiero Norfo, Dr. Lara Tavernari, Prof. Rossella Manfredini, Dr. Sebastiano Rontauroli.

Categorie: International - english

Articolo pubblicato da: Ufficio Stampa Unimore - ufficiostampa@unimore.it il 09/07/2024