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Cancers 2019, 11(2), 176; https://doi.org/10.3390/cancers11020176

Releasing the Immune System Brakes Using siRNAs Enhances Cancer Immunotherapy

Department of Immunology, Institute for Cancer Research, Oslo University Hospital-Radiumhospitalet, Montebello, N-0310 Oslo, Norway
Received: 6 January 2019 / Revised: 29 January 2019 / Accepted: 31 January 2019 / Published: 3 February 2019
(This article belongs to the Special Issue Cancer Vaccines: Research and Applications)
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Abstract

Therapeutic dendritic cell (DC) cancer vaccines rely on the immune system to eradicate tumour cells. Although tumour antigen-specific T cell responses have been observed in most studies, clinical responses are fairly low, arguing for the need to improve the design of DC-based vaccines. The incorporation of small interfering RNAs (siRNAs) against immunosuppressive factors in the manufacturing process of DCs can turn the vaccine into potent immune stimulators. Additionally, siRNA modification of ex vivo-expanded T cells for adoptive immunotherapy enhanced their killing potency. Most of the siRNA-targeted immune inhibitory factors have been successful in that their blockade produced the strongest cytotoxic T cell responses in preclinical and clinical studies. Cancer patients treated with the siRNA-modified DC vaccines showed promising clinical benefits providing a strong rationale for further development of these immunogenic vaccine formulations. This review covers the progress in combining siRNAs with DC vaccines or T cell therapy to boost anti-tumour immunity. View Full-Text
Keywords: dendritic cells; immunotherapy; gene silencing; adoptive cell therapy; RNA interference; targeted therapies; checkpoint inhibitors dendritic cells; immunotherapy; gene silencing; adoptive cell therapy; RNA interference; targeted therapies; checkpoint inhibitors
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Sioud, M. Releasing the Immune System Brakes Using siRNAs Enhances Cancer Immunotherapy. Cancers 2019, 11, 176.

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