Abstract 4506
Background
Oncolytic viruses constitute a promising modality of cancer therapy. Pexa-Vec, a Thymidine Kinase-Deactivated Vaccinia Virus expressing GM-CSF, has been shown to target tumor tissue after intravenous (i.v.) administration (Breitbach C.J. et al., 2011). Herein, we report on the immunostimulatory effects of Pexa-Vec prior to surgical resection in patients with advanced solid tumors.
Methods
Patients with operable tumors (3 with metastatic melanoma and 6 with colorectal cancer metastases to the liver (CRLM)) received a single i.v. dose of 1x109 plaque forming units of Pexa-Vec, approximately 14 days prior to surgical resection. Translational and histologic assessment was performed on blood samples collected pre- and post-injection and tumor collected at surgery.
Results
Pexa-Vec injection was well tolerated in all cases. Pexa-Vec was detected in serum immediately after iv administration but not in PBMC. Histologic examination of tumor tissue indicates the presence of virus in tumor at the time of surgery 14 days after administration. Of the 4 evaluable CRLM, one showed complete necrosis, and another partial necrosis, within a normal background liver. Analysis of peripheral blood mononuclear cells and tumor infiltrating lymphocytes showed robust activation of Natural Killer (NK) cells and CD8+ cells, with high CD69 and PD-L1 expression. Functional assays revealed increased NK cell degranulation and elevated tumor-associated antigen recognition by T cells. Furthermore, Pexa-Vec induced a significant elevation of serum cytokines associated with immune response including IFNα, IFNβ, TRAIL and CXCL10.
Conclusions
When administered intravenously, Pexa-Vec exhibited a selective persistence in tumor suggesting a tumor-targeted oncolytic action. Concurrently, Pexa-Vec triggered a robust immune activation of both innate and adaptive immune cells and infiltration of lymphocytes into tumor, associated with extensive necrosis in some patient tumours. These data strongly support the rationale for sequential i.v. use of oncolytic vaccinia virus in combination with immune checkpoint modulation therapy.
Clinical trial identification
ISRCTN13913966.
Editorial acknowledgement
Legal entity responsible for the study
University of Leeds.
Funding
Transgene.
Disclosure
A. Samson: Research grant / Funding (institution): Transgene. K. Bendjama: Full / Part-time employment: Transgene. N. Stojkowitz: Full / Part-time employment: Transgene. M. Lusky: Full / Part-time employment: Transgene. A. Melcher: Research grant / Funding (institution): Transgene. F. Collinson: Research grant / Funding (institution): Transgene. All other authors have declared no conflicts of interest.
Resources from the same session
5383 - A pilot trial to investigate the impact of a personalised self-management lifestyle programme using mobile technology on the health and wellbeing of cancer survivors
Presenter: Mary Grace Kelly
Session: Poster Display session 3
Resources:
Abstract
5084 - The BRIGHTLIGHT national survey of the impact of specialist teenage and young adult cancer care on caregivers’ information and support needs
Presenter: Rachel Taylor
Session: Poster Display session 3
Resources:
Abstract
4328 - Life beyond cancer: Occupational health care service support in returning work experienced by cancer survivals
Presenter: Minna Nurmi
Session: Poster Display session 3
Resources:
Abstract
3337 - Investigating the factors related to primary caregivers' burden in oncology patients in Greece
Presenter: Ourania Govina
Session: Poster Display session 3
Resources:
Abstract
3387 - Factors Influencing the Level of Emotional Support from Nurses Perceived by Patients Undergoing Haematopoietic Stem Cell Transplantation in Protective Isolation
Presenter: Michela Piredda
Session: Poster Display session 3
Resources:
Abstract
935 - Progressive Muscle Relaxation and Guided Imagery Techniques and the Way of Coping of Parents of Children with Malignancies: A randomized controlled trial
Presenter: Tsitsi Theologia
Session: Poster Display session 3
Resources:
Abstract
3457 - Pharmacist and Nurse Led Melanoma Immunotherapy Clinic
Presenter: Dharmisha Chauhan
Session: Poster Display session 3
Resources:
Abstract
5160 - Measuring the impact of the Irish Cancer Society's Cancer Information Services
Presenter: Aileen McHale
Session: Poster Display session 3
Resources:
Abstract
4297 - It's Great to Talk
Presenter: Noreen Andersen
Session: Poster Display session 3
Resources:
Abstract
4444 - Impact of Burn-Out Syndrome in Oncology personnel and its improvement through specific interventions
Presenter: Inmaculada Ortega
Session: Poster Display session 3
Resources:
Abstract