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Immunization with virus-modified tumor cells
V Schirrmacher1, T Ahlert, T Pröbstle
1Abteilung Zelluläre Immunologie (G0100), Deutsches Krebsforschungszentrum, Heidelberg, Germany.
Abstract:
Direct infection of tumor cells with viruses transfering protective or therapeutic genes-a frequently used procedure for production of tumor vaccines in human gene therapy-is often limited by the number of tumor cells that can reliably be infected, as well as by issues of selectivity and safety. In this review, we describe an efficient, selective, and safe way of infecting human tumor cells with a natural virus with interesting pleiotropic immune stimulatory properties, the avian paramyxovirus Newcastle disease virus (NDV). Advantages of this virus are its good cell-binding properties, its selective replication in tumor cell cytoplasm, which is independent of cell proliferation, and its relative safety. Most important for its use as an adjuvant in human cancer vaccine are its ability to introduce T-cell costimulatory activity, to prevent anergy induction, and to induce locally chemokines (eg, RANTES, IP-10) and cytokines (eg, interferon alpha, beta [IFN-alpha, beta] and tumor necrosis factor-alpha [TNFalpha]) that affect T-cell recruitment and activation. A further development consists of attachment-via NDV-derived hemagluttinin-neuraminidase (HN) membrane-anchoring molecules-of universal defined bispecific reagents such as T-cell-activating anti-CD28 antibodies. Finally, we summarize the status of our clinical studies with the autologous virus modified live cell vaccine (ATV)-NDV.
Insights
Newcastle disease virus (NDV) offers an efficient, safe method for infecting tumor cells in gene therapy. This natural virus enhances cancer vaccines by stimulating immune responses and recruiting T-cells.
Area of Science:
- Oncolytic virology
- Immunotherapy
- Gene therapy
Background:
- Direct tumor cell infection for gene therapy vaccines faces limitations in efficiency, selectivity, and safety.
- Newcastle disease virus (NDV), an avian paramyxovirus, possesses intrinsic immune-stimulating properties beneficial for cancer therapy.
Purpose of the Study:
- To review the use of Newcastle disease virus (NDV) for efficient, selective, and safe infection of human tumor cells.
- To highlight NDV's potential as an adjuvant in cancer vaccines by modulating immune responses.
Main Methods:
- Utilizing NDV's natural cell-binding and selective cytoplasmic replication properties.
- Exploring NDV's ability to induce T-cell costimulatory activity and prevent anergy.
- Investigating NDV's capacity to recruit immune cells via chemokine and cytokine induction (RANTES, IP-10, IFN-α/β, TNF-α).
Main Results:
- NDV demonstrates good cell-binding and selective replication in tumor cells, independent of proliferation.
- NDV enhances anti-tumor immunity by promoting T-cell activation and recruitment.
- Attachment of bispecific reagents via NDV's HN molecule offers further therapeutic potential.
Conclusions:
- NDV presents a promising platform for oncolytic virotherapy and cancer vaccine development.
- NDV's immunomodulatory effects make it a valuable adjuvant for enhancing cancer treatment strategies.
- Clinical studies with autologous virus modified live cell vaccine (ATV)-NDV are ongoing.