Adoptive immunotherapy combined with intratumoral TLR agonist delivery eradicates established melanoma in mice
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
Cancer Immunology, Immunotherapy | SPRINGER | Published : 2011
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 subcutaneou..View full abstract
Awarded by NATIONAL CANCER INSTITUTE
This work was supported by the National Health and Medical Research Council of Australia (NHMRC), Cancer Council of Victoria and The Bob Parker Memorial Fund. M.K. is supported by a Senior Research Fellowship from the NHMRC. P.D. is supported by an NHMRC Career Development Award, M.J.S. is supported by an Australia Fellowship from the NHMRC and S.A. is supported by a Cancer Council of Victoria Postgraduate Cancer Research Scholarship.