Intravenous Oncolytic Vaccinia Virus Therapy Results in a Differential Immune Response between Cancer Patients.
Date
2022-04-27ICR Author
Author
West, EJ
Scott, KJ
Tidswell, E
Bendjama, K
Stojkowitz, N
Lusky, M
Kurzawa, M
Prasad, R
Toogood, G
Ralph, C
Anthoney, DA
Melcher, AA
Collinson, FJ
Samson, A
Type
Journal Article
Metadata
Show full item recordAbstract
Pexa-Vec is an engineered Wyeth-strain vaccinia oncolytic virus (OV), which has been tested extensively in clinical trials, demonstrating enhanced cytotoxic T cell infiltration into tumours following treatment. Favourable immune consequences to Pexa-Vec include the induction of an interferon (IFN) response, followed by inflammatory cytokine/chemokine secretion. This promotes tumour immune infiltration, innate and adaptive immune cell activation and T cell priming, culminating in targeted tumour cell killing, i.e., an immunologically 'cold' tumour microenvironment is transformed into a 'hot' tumour. However, as with all immunotherapies, not all patients respond in a uniformly favourable manner. Our study herein, shows a differential immune response by patients to intravenous Pexa-Vec therapy, whereby some patients responded to the virus in a typical and expected manner, demonstrating a significant IFN induction and subsequent peripheral immune activation. However, other patients experienced a markedly subdued immune response and appeared to exhibit an exhausted phenotype at baseline, characterised by higher baseline immune checkpoint expression and regulatory T cell (Treg) levels. This differential baseline immunological profile accurately predicted the subsequent response to Pexa-Vec and may, therefore, enable the development of predictive biomarkers for Pexa-Vec and OV therapies more widely. If confirmed in larger clinical trials, these immunological biomarkers may enable a personalised approach, whereby patients with an exhausted baseline immune profile are treated with immune checkpoint blockade, with the aim of reversing immune exhaustion, prior to or alongside OV therapy.
Collections
Subject
biomarkers
differential immune response
immune checkpoint blockade
immune exhaustion
immunotherapy
interferon response
oncolytic virus therapy
vaccinia virus
Research team
Trans Immunotherapy
Language
eng
Date accepted
2022-04-15
License start date
2022-04-27
Citation
Cancers, 2022, 14 (9), pp. 2181 -
Publisher
MDPI