Mastodawn

Oncolytic viruses looked promising, but trials showed they could not eradicate metastasis. New experiments reveal why: they prime T cells against the virus, not the cancer.

#cancer
#immunotherapy
#oncolytic

https://www.biorxiv.org/content/10.1101/2025.09.22.677905v1

The anti-virus T cell response dominates the anti-cancer response in oncolytic virus therapy

Oncolytic viruses have strong potential as immunotherapies. By causing cancer cells to die and relieve antigens, these viruses can stimulate robust, systemic immune responses that may eliminate disseminated disease and prevent recurrence. Unfortunately, clinical trials using oncolytic viruses have not induced clearance of metastasis or protection from recurrence. Likewise, the combination of the only FDA-approved oncolytic virus-Talimogene laherparapvec-with immune checkpoint blockade did not improve progression-free or overall survival. Because of these disappointing clinical trials, we sought to measure the ability of oncolytic viruses to induce cancer antigen presentation and the elicitation of cancer antigen-specific immune responses. Our data revealed that despite improved antigen presentation by dendritic cells, priming of cancer antigen-specific T cells was limited. However, viral antigen-specific T cells did develop and were in a phenotypic state to induce an effective response against virally infected cells. These preclinical results were mirrored in human peripheral blood samples. Overall, these data show that oncolytic virus treatment induces a response against the virus itself, but not cancer antigen, explaining the lack of response in metastatic disease. These interesting findings identify a critical mechanism that needs to be overcome to increase the efficacy of oncolytic virus therapy. ### Competing Interest Statement The authors have declared no competing interest. National Institutes of Health, https://ror.org/01cwqze88, F32CA275298, R21AG072205, R01CA214913, R01HL128168, R01CA284603, R01CA247441 National Institutes of Health, R01CA247441, U01CA261842, R01CA284603 Massachusetts General Hospital, https://ror.org/002pd6e78

bioRxiv

Scientific Frontline May 15, 2023

#Intratumoral delivery of an #engineered #oncolytic #virus (DNX-2401) targeting #glioblastoma (#GBM ) cells combined with subsequent #immunotherapy was safe and improved survival outcomes in a subset of patients with recurrent GBM
#Cancer #Medical #Neuroscience #sflorg
https://www.sflorg.com/2023/05/med05152301.html

Combined delivery of engineered virus with immunotherapy is safe and improves outcomes in subset of patients with glioblastoma

Study validates safety of combination approach, offering possibilities to adapt treatment strategies to optimize outcomes

thijsjanzen Dec 26, 2022

In time for Christmas 🎄 our mathematical modeling of #Oncolytic #virotherapy in presence of resistant cells, is online

Big cheers to all the coauthors, #DarshakBhatt, #ToosDaemen and #FranjoWeissing
Link: https://doi.org/10.1371/journal.pcbi.1010076

Modelling the spatial dynamics of oncolytic virotherapy in the presence of virus-resistant tumour cells

Author summary Oncolytic virotherapy is a promising form of cancer treatment that uses viruses to target, infect and kill cancer cells. Unfortunately, this form of therapy is often not effective, due to the occurrence of virus-resistant tumor cells. As it is challenging to assess the emergence and spread of resistance experimentally or in (pre)clinical studies, we designed a model that allows to study the spatial dynamics of virus-sensitive and virus-resistant tumor cells in various scenarios, and to predict the efficacy of virotherapy. By analysing the model systematically, we demonstrate the importance of 2D and 3D spatial interactions, the effects of viral properties (such as replication rate and range of infection), the properties of virus-resistant cancer cells (such as the cost of resistance), and the sensitivity of healthy (non-tumor) cells towards viral infection. Our goal is to provide a sound conceptual understanding of the mechanisms underlying therapeutic failure, which eventually may lead to the discovery of strategies that improve therapeutic efficacy. We therefore provide the reader with a graphical and a terminal interface of our model (executable on a local computer), allowing practitioners to reflect on their intuition regarding the complex yet fascinating dynamics of oncolytic virotherapy.