Projects in collaboration with other IEO Units

Optimization of a Clinical Genomics platform for the identification of molecular markers of drug sensistivity and of inhereited genetic variants associated with cancer risk.

In collaboration with the Clinical Genomics Lab

Inherited genetic variants are known to predispose to cancer and specific somatic mutations predict the response to drugs ("actionable" mutations), allowing for the design of personalized therapeutic schemes. One of the difficulties in translating these discoveries into concrete benefits for cancer patients is that currently the diagnostic pathways for identifying hereditary variants and somatic mutations remain distinct. One generic objective of this Unit is therefore to set-up and optimize diagnostic platforms for the simultaneous identification of somatic mutations in actionable genes (for prognosis and therapy) and hereditary variants in cancer predisposing genes (for mapping genetic cancer risk).

Autologous transplantation of cytokine-induced killer cells expressing Interleukin 12 for cancer therapy.

In collaboration with the IEO Division of Hematology

Preclinical studies in humans and mice have shown that Interleukin 12 (IL-12) possesses a strong antitumor activity in many cancer types, both solid and hematologic, but effective doses are often associated with a marked and unpredictable toxicity. While IL-12 efficacy correlates with its concentration in tumor tissue, toxicity appears to be related to its concentration in peripheral blood. In addition, it has been shown that cell-bound IL-12 retains the antitumor activity of the secreted form but is only traceable in the bloodstream and does not cause systemic toxicity. One possibility to reach high intra-tumoral IL-12 concentration is represented by the use of Cytokine-Induced Killer (CIK) cells, capable of migration into tumors. It is hypothesized that CIK-IL12 cells will accumulate in tumors and exhibit a potent anticancer activity. The aim of this project is to characterize the anticancer activity of CIK cells expressing IL-12 against metastatic melanoma, colon carcinoma and reticular lymphoma. Following the validation of the effectiveness of this model, further development of this strategy involving human IL-12 and human CIK cells is foreseen. Indeed, this project will permit to obtain advantages in terms of tumor size reduction and regression by harnessing the immune system in an anti-tumor sense upon contact of IL-12 with tumor antigens.