A chimeric oncolytic virus and T cells for cancer immunotherapy.


An innovative method called ONCOTECH has been developed by researchers to physically attach oncolytic adenoviruses to T-cell surfaces through the interaction of antigen and receptors. To accomplish this, viruses, which encode the Cas9 system that targets immune checkpoint inhibitor genes, are enveloped in cell membranes that bear T-cell-specific antigens and delivered intravenously into the tumor. . This combination of virotherapy and cell therapy with ONCOTECH represents a promising translational technology.

Research Article,”An oncolytic virus-T cell chimera for cancer immunotherapy,Posted in nature biotechnology,

ONCOTECH enhances antitumor responses

Among the new forms of immunotherapy for cancer treatment, oncolytic virotherapy is prominent. Oncolytic viruses can kill tumor cells without spreading to healthy tissues because they replicate only in tumor cells after intratumoral administration, triggering tumor-specific inflammatory responses. However, several challenges are limiting the technology.

Systemic delivery of oncolytic viruses is more practical for clinical indications and can easily target primary and disseminated tumors, although intratumoral delivery guarantees direct access to tumor lesions and avoids potential systemic neutralization. However, due to insufficient virus uptake by tumor cells, intravascular administration of oncolytic viruses has not shown significant antitumor activity. Another drawback of oncolytic virotherapy is upregulation of immune checkpoints (such as PD-L1) in cancer and healthy immune cells. Two possible solutions are to combine oncolytic viruses with immune checkpoint inhibitors or to add anti-PD-L1 antibodies. However, oncolytic viruses and immune checkpoint inhibitors still have problems entering tumors; Therefore, new methods are needed to target tumors with these agents.

Researchers from Zhejiang University and the Chinese Academy of Sciences created ONCOTECH. This system relies on an oncolytic virus enveloped in a synthetic biological membrane that bears T-cell-specific antigens. T cells physically bind oncolytic viruses to their surfaces through their receptors, which can be TCRs or chimeric antigen receptors (CARs), without affecting cell function. With the help of carrier T cells that have recognized tumor-specific antigens, oncolytic viruses can be easily released and internalized by cancer cells, allowing targeted viral infection. Oncolytic viruses engineered to express the Cas9 editor can reduce PD-L1 expression in tumor cells and infiltrating immune cells following infection. It reduces the immunosuppressive tumor microenvironment and improves the effectiveness of T-cell therapy and oncolysis in fighting tumors.

Several limitations of ONCOTECH must be addressed to move forward with clinical translation in the future. One issue is that tumor antigens on biological membranes can repeatedly stimulate TCR or CAR, depleting T cells and impairing their ability to perform effector functions. To overcome this, carrier T cells can be engineered to express CARs with dual specificities. Additionally, it is not currently possible to use ONCOTECH to treat antigen-deficient or antigen-deficient advanced solid tumors; However, this is not an issue when treating melanoma, lung cancer, PDAC, or glioblastoma, all of which are tumors that express the antigen. Finally, clinical translation may be hindered due to immune incompatibility between the recipient and the cells used to produce the vesicles. Future research should focus on developing production cells compatible with the immune system to avoid potential immunological rejection by patients. This will help it avoid detection by host immune cells, such as NK cells, before viral infection occurs.



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