Molecule Unmasks Tumors

Modify the tumor to make it more visible to the immune system ‘eyes’. A pioneering study by the Immuno-oncology Center (IOC) of the Santa Maria alle Scotte polyclinic in Siena, directed by Michele Maio, opens the door to the current challenge of oncology, that of increasing the number of patients who respond positively to immunotherapy. The results of the Nibit-M4 study will be presented in world preview tomorrow at the Asco (American Society of Clinical Oncology) in Chicago.

The current challenge in the fight against cancer is to increase the number of patients who respond positively to immunotherapy. To do this it is necessary to ‘prepare’ the tumor to be recognized more effectively by the immune system.

The research team led by Michele Maio, in collaboration with important Italian and European centers, “has shown that in patients with melanoma the sequence of guadecitabine and ipilimumab – the former a hypomethylating agent, the latter an immunotherapy – improves the capacity of the immune system to recognize and attack cancer cells, “stresses the note from the Nibit Foundation. The phase 1b study, which began in 2015 and involved 19 patients with metastatic melanoma, first of all achieved the objective of demonstrating the safety and tolerability of the two drug administration sequence. Analyzes also revealed that 42% of patients had disease control and an objective response to treatment in 26% of cases, “highlights the Nibit Foundation.

In the past ten years, immunotherapy has revolutionized cancer treatment. “Some neoplasms that left no way out today can be successfully treated, but only about 40-50% of patients respond to this type of treatment – the experts underline – If on the one hand one of the possible strategies to increase the percentage is to improve the sequence with which to administer the various immunotherapics, the other involves the administration of immunotherapy in combination with molecules capable of modifying the characteristics of the tumor, with the aim of making it more visible to the immune system. direction”.

Not only. The analyzes carried out on the patient’s tumor samples have shown that the use of guadecitabine has led to a greater expression of those genes involved in the recognition between tumor and immune system, a clear proof of the goodness of the method used “.

The strategy used involved the administration of an epigenetic drug, guadecitabine, capable of determining chemical changes in the DNA of cancer cells in order to modulate their gene expression. “The changes generated by this drug – explains Alessia Covre, coordinator of the IOC pre-clinical research at the Policlinico Santa Maria alle Scotte in Siena, co-author of the study – mean that cancer cells express, on their surface, molecules that have a role fundamental in the interaction between tumor and immune system. Thus the tumor is more visible to the ‘eyes’ of the cells of the patient’s immune system and guadecitabine creates the optimal conditions to ensure that the immunotherapy drugs administered subsequently can have greater efficacy “.