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01.05.2011 | Original article

Adoptive immunotherapy combined with intratumoral TLR agonist delivery eradicates established melanoma in mice

verfasst von: Sally M. Amos, Hollie J. Pegram, Jennifer A. Westwood, Liza B. John, Christel Devaud, Chris J. Clarke, Nicholas P. Restifo, Mark J. Smyth, Phillip K. Darcy, Michael H. Kershaw

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 5/2011

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Abstract

Toll-like receptor (TLR) agonists can trigger broad inflammatory responses that elicit rapid innate immunity and promote the activities of lymphocytes, which can potentially enhance adoptive immunotherapy in the tumor-bearing setting. In the present study, we found that Polyinosinic:Polycytidylic Acid [Poly(I:C)] and CpG oligodeoxynucleotide 1826 [CpG], agonists for TLR 3 and 9, respectively, potently activated adoptively transferred T cells against a murine model of established melanoma. Intratumoral injection of Poly(I:C) and CpG, combined with systemic transfer of activated pmel-1 T cells, specific for gp100_25–33, led to enhanced survival and eradication of 9-day established subcutaneous B16F10 melanomas in a proportion of mice. A series of survival studies in knockout mice supported a key mechanistic pathway, whereby TLR agonists acted via host cells to enhance IFN-γ production by adoptively transferred T cells. IFN-γ, in turn, enhanced the immunogenicity of the B16F10 melanoma line, leading to increased killing by adoptively transferred T cells. Thus, this combination approach counteracted tumor escape from immunotherapy via downregulation of immunogenicity. In conclusion, TLR agonists may represent advanced adjuvants within the setting of adoptive T-cell immunotherapy of cancer and hold promise as a safe means of enhancing this approach within the clinic.

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Titel: Adoptive immunotherapy combined with intratumoral TLR agonist delivery eradicates established melanoma in mice
verfasst von: Sally M. Amos
Hollie J. Pegram
Jennifer A. Westwood
Liza B. John
Christel Devaud
Chris J. Clarke
Nicholas P. Restifo
Mark J. Smyth
Phillip K. Darcy
Michael H. Kershaw
Publikationsdatum: 01.05.2011
Verlag: Springer-Verlag
Erschienen in: Cancer Immunology, Immunotherapy / Ausgabe 5/2011
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-011-0984-8

Springer Medizin

Adoptive immunotherapy combined with intratumoral TLR agonist delivery eradicates established melanoma in mice

Abstract

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Springer Medizin

Abstract

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