We Have Enrolled the First Patient in the Raffaello-Res Randomized Study!

Monoclonal antibodies that block immune checkpoints have revolutionized cancer treatment for patients with metastatic melanoma. One such antibody (anti-PD1) significantly improves overall survival, but a substantial proportion of patients remain resistant to immunotherapy.

One mechanism responsible for PD-1 resistance is the reduced expression of class I HLA molecules, which prevents the presentation of tumor antigens. These HLA molecules enable tumor cells to be recognized by T lymphocytes—immune system warriors capable of identifying and eliminating cancer cells.

HLA molecules can be thought of as "flags" that signal to immune cells, reactivated by immunotherapy, which cells should be targeted for destruction. The microbiota (formerly known as gut flora) has been recognized for its influence on the response
to immunotherapy.

In a previously project funded by the Alan Ghitis Association, we demonstrated in preclinical models that certain bacterial metabolites (postbiotics) produced by a specific strain of Lactobacillus paracasei increase the expression of class I HLA molecules on tumor cells, making them visible again to T cells*.

In this randomized phase II clinical study cofunded by the Alan Ghitis Association, approved by the Ethics Committee of the University of Perugia, we aim to prove that a similar mechanism occurs in patients with metastatic melanoma. This study combines anti-PD1 treatment with postbiotics in patients who have not responded to immunotherapy, to determine whether postbiotics can induce HLA I molecule expression on tumor cells and restore patient responsiveness to immunotherapy.
We have already enrolled our first patient!

This exciting study could open new possibilities for overcoming resistance to immunotherapy in melanoma patients!