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Oncolytic immunotherapy is a cancer treatment that uses the viruses that mediate antitumor activity to induce immunogenic cell death and generate an immunity against tumors.
The Oncolytic Virus Laboratory at Massachusetts General Hospital is using animal models and human clinical trials, with a particular focus on the herpes simplex virus, to better understand and improve oncolytic immunotherapy.
The goals of the Oncolytic Virus Lab are to:
Combining three treatment strategies may significantly improve melanoma treatmentDecember 2018A study by a team led by Howard Kaufman, MD, FACS, finds evidence that combining three advanced treatment strategies for malignant melanoma - molecular targeted therapy, immune checkpoint blockade and the use of tumor-targeting viruses - may markedly improve outcomes.
2018 Journal for ImmunoTherapy of Cancer (JITC) Best Clinical/Translational Paper AwardNovember 2018A manuscript from the Oncolytic Virus Lab titled “Durable response rate as an endpoint in cancern immunotherapy: insights from oncolytic virus clinical trials” was named best clinical/translational research paper of 2018 at the JITC’s annual Society for Immunotherapy of Cancer meeting in Washington, DC.
The Oncolytic Virus Lab is directed by Howard Kaufman, MD, FACS, a surgeon in the Mass General Department of Surgical Oncology. Dr. Kaufman is a physician-scientist and leading authority on oncolytic tumor immunotherapy, pioneering the first oncolytic virus therapy for the treatment of melanoma and the first immunotherapy for treating Merkel cell carcinoma.
Biomarkers of Oncolytic ImmunotherapyThe importance of predictive biomarkers to better select appropriate patients for immunotherapy as well as for identifying putative mechanisms of resistance has been emphasized as a high priority for the field. Ongoing projects are utilizing patient-derived biospecimens to explore potential intracellular and peripheral biomarkers of response. In addition, we are employing novel technologies to explore genomic, proteomic and metabolomic factors that influence the therapeutic response to oncolytic virus immunotherapy. We work closely with the Drs. Sara Pai's and Ryan Sullivan's labs on these projects.
Combination Oncolytic ImmunotherapyA major focus of the lab is to develop innovative combination strategies wherein oncolytic viruses are used to induce lymphocyte recruitment and activation to sites of tumor growth and optimize combination regimens. This has included both animal models and human clinical trials. We established a role for combination of HSV-1 oncolytic virus with immune checkpoint blockade in clinical melanoma studies. In addition, we recently identified a new pathway where MEK inhibition augmented oncolytic virus replication and increased sensitivity of tumors to PD-1 blockade. These findings are being pursued in new clinical trials for patients with melanoma and other types of solid tumors.
Oncolytic Viruses Killing of Tumor CellsHow does oncolytic HSV-1 kill tumor cells and induce immunogenic cell death? Studies in the lab have focused on the role of apoptosis and other forms of cell death, such as autophagy, in mediating cell death. We have also demonstrated the release of danger-associated molecular pattern (DAMP) factors following oncolytic virus infection. In addition, we have explored how specific elements of the antiviral machinery, such as STING, can influence viral replication and induction of host immune responses.
Oncolytic Virus-induced AntiTumor ImmunityThe clearance of tumor depends on the balance between anti-viral and anti-tumor immunity. The lab has established numerous models to explore how innate and adaptive immunity responds to oncolytic immunotherapy. We are also exploring the mechanisms of local immunity at sites to intratumoral virus delivery compared to induction of systemic anenestic responses that occur at distant, uninjected tumor sites.
Oncolytic Virus LaboratoryDepartment of Surgical OncologyMassachusetts General HospitalWarren 408C55 Fruit StreetBoston, MA 02114
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