OCT 16, 2013 2:00 PM PDT

Novel therapies for ALK mutated cancers

C.E. Credits: CE
Speaker
  • Associate Professor in Pathology, Harvard Medical School, Department of Pathology, Children's Hospital Boston
    Biography
      Roberto Chiarle received an M.D. degree from the University of Turin, Italy. Then, he earned a Board in Surgical Pathology from the University of Torino. He did his postdoc research training with Giorgio Inghirami and Michele Pagano at the New York University, where he worked on the molecular pathogenesis of B and T cell lymphomas. He was appointed as Assistant Professor in Pathology and as Attending Physician in Pathology in the University of Turin, Italy in 1999, then promoted to Associate Professor in 2006. In Italy, he started his own lab and worked on the ALK oncogene in human lymphoma, to discover new molecular mechanisms of ALK mediated cell transformation and new ALK specific therapies. From 2008 to 2010, he was Visiting Professor in Pathology in Fred W. Alt lab at the Immune Disease Institute/Childrens Hospital, Boston, where he worked on chromosomal translocations and contributed to develop a new high-throughput method to clone translocations genome-wide from primary B cells. In 2012, he was appointed as Associate Professor of Pathology at Harvard Medical School and started his own lab at the Childrens Hospital Boston. He won numerous grants and awards in Europe, such as the Italian National Premio Sapio Junior Investigator Award, the Italian National prize Carlo Chianello Foundation Research Award, the prestigious ERC Starting Grant from the European Research Council and the research award from the Association for International Cancer Research, UK.

    Abstract

    Non Small Cell Lung Cancer (NSCLC) is one of the most significant causes of cancer-related mortality worldwide. In about 6-7% of NSCLC, rearrangements involving the Anaplastic Lymphoma Kinase (ALK) play a strong driver role in tumor progression. Indeed, blocking ALKs kinase activity with the use of selective kinase inhibitors, such as crizotinib, induces an exceptionally high rate of clinical responses in ALK-rearranged NSCLC. Unfortunately, almost all patients relapse due to resistance to crizotinib developed in tumors by various molecular mechanisms. Therefore, developing additional therapeutic options for ALK-rearranged NSCLC is a pressing clinical need. The ALK protein has many, quite unique, features of an ideal tumor onco-antigen: it is specifically expressed by tumor cells with very low and limited expression in normal tissues, it is naturally immunogenic in humans, as indicated by studies on patients with ALK-rearranged tumors, and it is required for tumor survival and growth, which greatly decreases the chances of ALK negative clones to escape the immune system. In preclinical experiments in mouse models of ALK-driven cancers, we demonstrated that DNA-based ALK vaccine elicited a specific and powerful immune response against the ALK protein that was sufficient to strongly reduce the growth of ALK-rearranged lymphoma and lung carcinoma. Based on this data, we predict that a highly potent and safe ALK-targeted vaccine will be beneficial for the treatment of lung cancer and lymphoma patients. In principle, this vaccine could be extended to any ALK-expressing cancer.


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