Massimo Aglietta
Full Professor
Contacts:
E-mail: massimo.aglietta@unito.it
Office: 0119933628 Fax: 0119933299
Department of Oncology
Immunotherapy and molecular targeted approaches in solid tumors: preclinical models and potential synergisms
Research Program
Conventional chemotherapy reached an unsatisfactory therapeutic plateau in the majority of metastatic solid tumors. New molecular targeted approaches improved the rates of cure in selected types of cancers but failed to eradicate the disease. A crucial issue that recently emerged is the presence of putative cancer stem cells, considered refractory to conventional treatments and responsible for relapses. New and synergic strategies, ideally capable of targeting CSCs, are needed.
Immunotherapy is currently considered among the most promising options for treatment for solid tumors and may offer intriguing opportunities for synergism with molecular targeted approaches. Our group in the last years contributed to the development of a new MHC-independent immunotherapy approach based on Cytokine-Induced Killer (CIK) cells and demonstrated its promising activity at preclinical level against solid tumors, including a subset of putative CSCs. A central aspect of our research model is a new generation, patient-specific preclinical model based on biological samples directly collected from our patients. The autologous platform is intended to account for the biologic and immunogenic variability of each single tumor and patient, resulting more representative of realistic clinical scenarios.
Main goal of our research program is to explore the preclinical activity of immunotherapy with Cytokine-Induced Killer (CIK) cells against metastatic solid tumors, focusing on putative CSCs and exploring potential synergism with the new molecular targeted approaches. Main but not exclusive cancer settings are metastatic melanoma, sarcomas, ovarian and biliary tract cancer.
Specific objectives are:
1) Generation and characterization of primary tumor cell cultures.
Tumor cell cultures will be generated from surgical samples directly collected from our patients. Main endpoints will be their phenotype and functional characterization in vitro and in vivo along with identification of putative CSCs.
2) Preclinical activity of immunotherapy against autologous solid tumors.
We will explore in vitro and in vivo the antitumor activity of CIK cells, expanded from patients against autologous tumor targets including CSCs.
3) Identification of druggable targets for treatment of solid tumors refractory to conventional therapies.
The study will aim to highlight mechanisms and markers associated to the occurrence of tumor resistance in patient-specific tumor preclinical models. This model will provide an experimental platform to investigate new molecular targeted approachesfor the treatment of solid tumors.
4) Synergism of immunotherapy with molecular targeted approaches.
We will explore the potential therapeutic synergism between immunotherapy with CIK cells and molecular targeted therapies, especially focusing on targeting CSCs and overcoming the resistance.
Research Products of Aglietta Massimo