Speaker Biography

Francesco Alessandrini

DiMES, Italy

Title: IL12 secreting retargeted fully virulent Herpes Simplex Virus as therapy for high-grade Glioma

Francesco Alessandrini


High Grade Gliomas (HGG) are the main malignant tumors of central nervous system and, so far, almost incurable because of the
radio- and chemo-resistance. A novel therapeutic approach, based on recombinant oncolytic Herpes Simplex Viruses (oHSV)
that target cells expressing specific receptors, combined with immunomodulation, fits in the field of new promising strategies aimed
at enhancing a targeted and efficient therapeutic response. We evaluated the effects of a retargeted fully virulent HSV-1 (named
R-115) armed with mIL12 on established syngeneic hHER2 expressing HGG. R-115 exhibited a specific hHER2 tropism. When
locally injected in large established gliomas, it is effective in counteract tumor growth, doubling the median survival after treatment
and we observe for the first time the appearance of long survivors associated with the development of the resistance to recurrence of
the same neoplasia. Retargeted viruses are intrinsically safer than attenuated ones and unlike other studies, we obtained a substantial
percentage of long survivors after a single injection of viral preparation into fully established gliomas that could potentially improve
with earlier or repeated treatments. Moreover, we pointed out that mIL12 expressing R-115 enhanced the production of antibodies
targeting transplanted glioma cells and it makes the tumor tissue accessible to infiltration of T-lymphocytes. Results obtained represent
a step forward towards the possibility to treat HGGs with retargeted oHSV.