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Adoptive T Cell Therapy Is Complemented by Oncolytic Virotherapy with Fusogenic VSV-NDV in Combination Treatment of Murine Melanoma

1
Klinik und Poliklinik für Innere Medizin II, Klinikum rechts der Isar, Technical University of Munich, 81675 Munich, Germany
2
Institut für Pathologie, Klinikum rechts der Isar, Technical University, 81675 Munich, Germany
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Comparative Experimental Pathology, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, Germany
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Klinik und Poliklinik für Innere Medizin III, Klinikum rechts der Isar, Technical University, 81675 Munich, Germany
5
German Cancer Consortium of Translational Cancer Research (DKTK) and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
*
Author to whom correspondence should be addressed.
Academic Editor: Antonio Marchini
Cancers 2021, 13(5), 1044; https://doi.org/10.3390/cancers13051044
Received: 29 January 2021 / Revised: 23 February 2021 / Accepted: 24 February 2021 / Published: 2 March 2021
(This article belongs to the Collection Advances and Future Prospects in Oncolytic Virus Immunotherapy)
Cancer immunotherapy involves the application of strategies aimed at enhancing the body’s immune system to recognize and clear tumor cells. One such immunotherapeutic approach utilizes cytotoxic immune cells (T cells) harvested from the patient, which are expanded and activated, followed by re-infusion to the same patient. This process is termed adoptive cell therapy (ACT). Although effective in a limited setting, efforts are being made to improve these therapies through the development of rationally designed combination treatments. We have developed an approach, whereby tumors are pretreated with a virus, which has oncolytic effects on the tumor cells, in addition to modulating changes in the tumor microenvironment, thereby improving the recruitment of the adoptively transferred cytotoxic T cells and resulting in synergistic therapeutic responses in the tumor. This results in a substantial prolongation of survival, as demonstrated in an immune-competent mouse model of melanoma.
Cancer immunotherapies have made major advancements in recent years and are becoming the prevalent treatment options for numerous tumor entities. However, substantial response rates have only been observed in specific subsets of patients since pre-existing factors determine the susceptibility of a tumor to these therapies. The development of approaches that can actively induce an anti-tumor immune response, such as adoptive cell transfer and oncolytic virotherapy, have shown clinical success in the treatment of leukemia and melanoma, respectively. Based on the immune-stimulatory capacity of oncolytic VSV-NDV virotherapy, we envisioned a combination approach to synergize with adoptive T cell transfer, in order to enhance tumor cell killing. Using the immune-competent B16 melanoma model, we demonstrate that combination treatment has beneficial effects on the suppressive microenvironment through upregulation of MHC-I and maintaining low expression levels of PD-L1 on tumor cells. The approach led to additive cytotoxic effects and improved the recruitment of T cells to virus-infected tumor cells in vitro and in vivo. We observed substantial delays in tumor growth and evidence of abscopal effects, as well as prolongation of overall survival time when administered at clinically relevant dosing conditions. Our results indicate that treatment with oncolytic VSV-NDV, combined with adoptive T cell therapy, induces multi-mechanistic and synergistic tumor responses, which supports the further development of this promising translational approach. View Full-Text
Keywords: cancer; immunotherapy; oncolytic virus; fusogenic; adoptive T cells; melanoma cancer; immunotherapy; oncolytic virus; fusogenic; adoptive T cells; melanoma
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MDPI and ACS Style

Krabbe, T.; Marek, J.; Groll, T.; Steiger, K.; Schmid, R.M.; Krackhardt, A.M.; Altomonte, J. Adoptive T Cell Therapy Is Complemented by Oncolytic Virotherapy with Fusogenic VSV-NDV in Combination Treatment of Murine Melanoma. Cancers 2021, 13, 1044. https://doi.org/10.3390/cancers13051044

AMA Style

Krabbe T, Marek J, Groll T, Steiger K, Schmid RM, Krackhardt AM, Altomonte J. Adoptive T Cell Therapy Is Complemented by Oncolytic Virotherapy with Fusogenic VSV-NDV in Combination Treatment of Murine Melanoma. Cancers. 2021; 13(5):1044. https://doi.org/10.3390/cancers13051044

Chicago/Turabian Style

Krabbe, Teresa, Janina Marek, Tanja Groll, Katja Steiger, Roland M. Schmid, Angela M. Krackhardt, and Jennifer Altomonte. 2021. "Adoptive T Cell Therapy Is Complemented by Oncolytic Virotherapy with Fusogenic VSV-NDV in Combination Treatment of Murine Melanoma" Cancers 13, no. 5: 1044. https://doi.org/10.3390/cancers13051044

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