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
5650 - Tissue-based activation of mucosal-associated invariant T (MAIT) cells in combination ipilimumab and nivolumab checkpoint inhibitor (CI) colitis.
Presenter: Sarah Sasson
Session: Poster Display session 3
Resources:
Abstract
5944 - Significance of severe immune-related adverse effects (irAE) on patients with advanced tumors treated with immune checkpoint inhibitors being admitted for secondary toxicity: Clinical relevance and next steps
Presenter: Leyre Zubiri
Session: Poster Display session 3
Resources:
Abstract
5989 - Implementation of a dedicated immuno-oncology toxicity service reduces the acute impact of immune-related adverse events
Presenter: Anna Olsson-Brown
Session: Poster Display session 3
Resources:
Abstract
3267 - Cardiotoxic and pro-inflammatory effects induced by the association of immune checkpoint inhibitor Pembrolizumab and Trastuzumab in preclinical models
Presenter: Nicola Maurea
Session: Poster Display session 3
Resources:
Abstract
3417 - Interstitial lung disease associated with immune-checkpoint inhibitors in malignant diseases
Presenter: Akira Yamagata
Session: Poster Display session 3
Resources:
Abstract
2071 - A Phase 1 Study of Intraperitoneal MCY-M11 Anti-Mesothelin CAR for Women with Platinum Resistant High Grade Serous Adenocarcinoma of the Ovary, Primary Peritoneum, or Fallopian Tube, or Subjects with Peritoneal Mesothelioma with Recurrence after Prior Chemotherapy
Presenter: Christina Annunziata
Session: Poster Display session 3
Resources:
Abstract
4935 - Trial in progress: First-in-human study of a novel anti-NY-ESO-1–anti-CD3, TCR-based bispecific (IMCnyeso) as monotherapy in NY-ESO-1/LAGE-1A-positive advanced solid tumors (IMCnyeso-101)
Presenter: Juanita Lopez
Session: Poster Display session 3
Resources:
Abstract
5613 - Nimotuzumab-Cisplatin-Radiation versus Cisplatin-Radiation in HPV negative oropharyngeal cancer
Presenter: Kumar Prabhash
Session: Poster Display session 3
Resources:
Abstract
2576 - Interim analysis of a single arm phase 2 study of adjuvant nivolumab after salvage resection in head and neck squamous cell carcinoma patients previously treated with definitive therapy.
Presenter: Trisha Wise-draper
Session: Poster Display session 3
Resources:
Abstract
4758 - A Phase I Study of the CDK4/6 Inhibitor, Palbociclib in combination with Cetuximab and Intensity Modulated Radiation Therapy (IMRT) for Locally Advanced Squamous Cell Carcinoma of the Head and Neck (SCCHN); A Result of Dose Escalation Cohort
Presenter: Nuttapong Ngamphaiboon
Session: Poster Display session 3
Resources:
Abstract