Line 2 – Immunology and immunotherapy of tumors

Description

This line of activity is focused on analyzing the interactions between immunity and cancer at two levels, systemic and of the neoplastic microenvironment, in particular as regards the development and evolution of the antitumor response, the avoidance mechanisms put in place by the neoplasm and the genetic / metabolic / cellular aspects underlying these events. A further aspect consists in identifying and implementing therapeutic solutions based on the most advanced technologies in the immune field and on the stimulation of the immunoeffective components, with the overall goal of restoring the full efficiency of the immune system and enhancing its anticancer capabilities.

Background

Cancer immunology is an interdisciplinary field of biology / medicine that aims to understand the changes occurring in the immune system during tumor development and progression. As it describes the interactions between immune cells and cancer cells, understanding these interactions is important for the development of new anticancer therapies. In this context, cancer immunotherapy is a rapidly evolving concept, so much so that it is defined as the “fifth pillar” of cancer therapy, in addition to radiotherapy, chemotherapy, surgery and targeted therapies. In this regard, the continuous expansion of the use of so-called immunological checkpoint inhibitors (ICI), monoclonal antibodies (mAb) able to prevent the feedback inhibition of activated T cells and to stimulate protective and therapeutic cellular T responses directed against neoantigens highly tumor-specific, also paves the way for further research areas such as:

• the profiling of the neoplastic component, for the identification of new targets, and of the immune infiltrate, for the characterization of the determinants of protection / efficacy;
• the development of strictly personalized immunotherapeutic interventions;
• the study of combinatorial therapies between ICI and pharmacological / nanotechnological, biotechnological, vaccine and / or adoptive therapies with T cells, capable of promoting the expansion and functionality of effector populations.

Rationale

The use of ICI in current oncological practice is literally revolutionizing the expectations of clinical outcome in many neoplastic areas, but on the other hand it increasingly imposes the identification of predictive biomarkers of response able to guide the selection of patients, in order to rationalize and personalize therapies keeping in mind both toxicity and cost-effectiveness profiles for the National Health System. On the other hand, the most recent evolutions in genomics, proteomics, metabolomics, etc., allow the acquisition of fundamental information to really envision the implementation of immunotherapeutic strategies at a strictly individual level. Finally, we must not forget the emerging role of adoptive cell therapy, in particular CAR-T, which from the haematological sector is rapidly finding experimental applications in solid tumors and in which IOV is particularly active, even with innovative effector cell populations.

Global Goals

Globally, the research line has multiple objectives, such as:

• the genetic / metabolic profiling, even single cell, of the neoplastic and infiltrative component of tumors potentially target of immunological therapies;
• cellular immunoprofilation at the peripheral level and in the tumor-stroma context with innovative techniques (multiparametric flow cytometry, multiplex fluorescence immunohistochemistry);
• the development of in vitro and in vivo experimental models for the understanding of tumor-immune system interactions and for the development and evaluation of newly conceived immunotherapeutic approaches.

Expected and measurable results over the three-year period

During the three-year period it is expected:

• to increase by at least 25% the number of profiled samples both at the genomic and immunophenotypic level and to arrive at a full integration between the data obtained in next generation sequencing, digital pathology and correlated with computerized clinical record, with the aim of identifying and validate new prognostic or predictive biomarkers of response;
• to increase by 20% the studies aimed at understanding the mechanisms and mediators involved in the avoidance of the immune response by the tumor, as well as possible reversal interventions;
• to enhance preclinical studies of active and adoptive immunotherapy, in order to identify at least two studies capable of being effectively translated into phase 1 clinical trials.