Limits...
Virus infections in tumors pave the way for tumor-directed DC-vaccines.

Woller N, Kühnel F, Kubicka S - Oncoimmunology (2012)

Bottom Line: Effective treatment of solid cancers by tumor-directed DC-vaccines still remains a challenge in clinical oncology.For therapeutic success, knock-down of tumor-specific tolerance appears mandatory before a potent tumor-specific cytotoxic T-cell response can be triggered by DC-vaccinations.Evidence is emerging that lytic virus infection in tumors can provide valuable help.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology, Hepatology and Endocrinology; Medical School Hannover; Hannover, Germany.

ABSTRACT
Effective treatment of solid cancers by tumor-directed DC-vaccines still remains a challenge in clinical oncology. For therapeutic success, knock-down of tumor-specific tolerance appears mandatory before a potent tumor-specific cytotoxic T-cell response can be triggered by DC-vaccinations. Evidence is emerging that lytic virus infection in tumors can provide valuable help.

No MeSH data available.


Related in: MedlinePlus

Figure 1. Schematic comparison of conventional and oncolysis-assisted DC-vaccination. In a conventional DC-vaccination (upper panel), a tumor-directed DC-vaccine is applied though a solid tumor mass is present in the patient. Consequently, tolerogenic properties of the tumor restrict efficient T cell priming. For oncolysis-assisted DC-vaccination (lower panel), a lytic virus infection is initiated in the tumor tissue to break tumor integrity and tolerance, and to provide tumor-associated antigens for cross presentation. Thus, onset of virus-mediated oncolysis and inflammation allows for efficient DC-vaccination.
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Figure 1: Figure 1. Schematic comparison of conventional and oncolysis-assisted DC-vaccination. In a conventional DC-vaccination (upper panel), a tumor-directed DC-vaccine is applied though a solid tumor mass is present in the patient. Consequently, tolerogenic properties of the tumor restrict efficient T cell priming. For oncolysis-assisted DC-vaccination (lower panel), a lytic virus infection is initiated in the tumor tissue to break tumor integrity and tolerance, and to provide tumor-associated antigens for cross presentation. Thus, onset of virus-mediated oncolysis and inflammation allows for efficient DC-vaccination.

Mentions: In a recent study,4 we investigated whether a tumor-directed DC-vaccination in tumor-bearing mice could provoke an effective antitumoral immune response, if the tumor is affected by a virus infection (Fig. 1). Injection of the telomerase-selectively replicating adenovirus hTert-Ad in subcutaneous tumors led to a fulminant but transient tumor inflammation characterized by lytic destruction of large tumor areas and massive lymphocyte infiltrations. Histologically, tumor inflammation was apparent at day 3 following virus injection. Virus clearance was then initiated and tumor recovery began. According to our hypothesis, a success of tumor-directed DC-vaccination, indicated by increasing numbers of tumor-directed CD8 T-cells, was only observable when the vaccine was given during apparent tumor inflammation. More important, the raised T-cell response led to a dramatically improved therapeutic outcome and even facilitated elimination of prestablished lung colonies, an important requirement for the treatment of disseminated diseases. Due to the correlation between oncolytic tumor inflammation and the success of vaccination we named this therapeutic regimen ‘oncolysis-assisted DC-vaccination’ (ODC). Observations that increased T-cell responses could be successfully raised against endogenous tumor-associated antigens such as telomerase and that antitumoral response increased at the expense of the virus-directed humoral response corroborated the physiologic relevance of ODC.


Virus infections in tumors pave the way for tumor-directed DC-vaccines.

Woller N, Kühnel F, Kubicka S - Oncoimmunology (2012)

Figure 1. Schematic comparison of conventional and oncolysis-assisted DC-vaccination. In a conventional DC-vaccination (upper panel), a tumor-directed DC-vaccine is applied though a solid tumor mass is present in the patient. Consequently, tolerogenic properties of the tumor restrict efficient T cell priming. For oncolysis-assisted DC-vaccination (lower panel), a lytic virus infection is initiated in the tumor tissue to break tumor integrity and tolerance, and to provide tumor-associated antigens for cross presentation. Thus, onset of virus-mediated oncolysis and inflammation allows for efficient DC-vaccination.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3377008&req=5

Figure 1: Figure 1. Schematic comparison of conventional and oncolysis-assisted DC-vaccination. In a conventional DC-vaccination (upper panel), a tumor-directed DC-vaccine is applied though a solid tumor mass is present in the patient. Consequently, tolerogenic properties of the tumor restrict efficient T cell priming. For oncolysis-assisted DC-vaccination (lower panel), a lytic virus infection is initiated in the tumor tissue to break tumor integrity and tolerance, and to provide tumor-associated antigens for cross presentation. Thus, onset of virus-mediated oncolysis and inflammation allows for efficient DC-vaccination.
Mentions: In a recent study,4 we investigated whether a tumor-directed DC-vaccination in tumor-bearing mice could provoke an effective antitumoral immune response, if the tumor is affected by a virus infection (Fig. 1). Injection of the telomerase-selectively replicating adenovirus hTert-Ad in subcutaneous tumors led to a fulminant but transient tumor inflammation characterized by lytic destruction of large tumor areas and massive lymphocyte infiltrations. Histologically, tumor inflammation was apparent at day 3 following virus injection. Virus clearance was then initiated and tumor recovery began. According to our hypothesis, a success of tumor-directed DC-vaccination, indicated by increasing numbers of tumor-directed CD8 T-cells, was only observable when the vaccine was given during apparent tumor inflammation. More important, the raised T-cell response led to a dramatically improved therapeutic outcome and even facilitated elimination of prestablished lung colonies, an important requirement for the treatment of disseminated diseases. Due to the correlation between oncolytic tumor inflammation and the success of vaccination we named this therapeutic regimen ‘oncolysis-assisted DC-vaccination’ (ODC). Observations that increased T-cell responses could be successfully raised against endogenous tumor-associated antigens such as telomerase and that antitumoral response increased at the expense of the virus-directed humoral response corroborated the physiologic relevance of ODC.

Bottom Line: Effective treatment of solid cancers by tumor-directed DC-vaccines still remains a challenge in clinical oncology.For therapeutic success, knock-down of tumor-specific tolerance appears mandatory before a potent tumor-specific cytotoxic T-cell response can be triggered by DC-vaccinations.Evidence is emerging that lytic virus infection in tumors can provide valuable help.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology, Hepatology and Endocrinology; Medical School Hannover; Hannover, Germany.

ABSTRACT
Effective treatment of solid cancers by tumor-directed DC-vaccines still remains a challenge in clinical oncology. For therapeutic success, knock-down of tumor-specific tolerance appears mandatory before a potent tumor-specific cytotoxic T-cell response can be triggered by DC-vaccinations. Evidence is emerging that lytic virus infection in tumors can provide valuable help.

No MeSH data available.


Related in: MedlinePlus