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Poster Presentation
Induction of systemic anti-melanoma immunity through intratumoral TLR-7/8 activation
  1. Manisha Singh1,
  2. Hiep Khong1,
  3. Zhimin Dai1,
  4. John P Vasilakos2,
  5. Patrick Hwu1 and
  6. Willem W Overwijk1
  1. Aff1 grid.240145.60000000122914776Department of Melanoma Medical OncologyThe University of Texas MD Anderson Cancer Center Houston TX USA
  2. Aff2 grid.417536.200000001069563193M Drug Delivery Systems Division3M Company St. Paul MN USA

https://doi.org/10.1186/2051-1426-2-S3-P176

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    Meeting abstracts

    Purpose

    Intratumoral immune activation can induce systemic immunity and anti-tumor activity. Imiquimod is a cream-formulated, TLR-7 agonist that is FDA-approved for the treatment of non-melanoma skin cancers, but has limited activity against melanoma. In the current study, we studied the anti-tumor activity and mechanism of action of a novel injectable TLR 7/8 dual agonist, 3M-052, which remains at the site of injection to avoid systemic distribution.

    Experimental design

    Mice bearing established B16 melanomas were treated intratumorally with 3M-052 or vehicle. The mechanistic contribution of individual cell types and molecules to the anti-tumor effect was determined using genetically engineered mice and antibody blockades. Immune cell infiltrates were analyzed by flow cytometry.

    Results

    Intratumoral administration of 3M-052 generated systemic anti-tumor immunity and suppressed both injected and distant uninjected wild-type B16.F10 melanomas. Treated tumors showed increased level of CCL2 chemokines and CCL2 dependent infiltration of M1 phenotype-shifted macrophages which could kill tumor cells directly through production of nitric oxide. CD8+ T cells, B cells, Type I IFN, IFN-g, and pDCs contributed to efficient tumor suppression whereas perforin, NK cells and CD4 T cells were not required.

    Conclusion

    Induction of effective innate and tumor specific adaptive immunity by intratumoral treatment of TLR7/8 agonist, 3M-052 is a promising approach for the treatment of metastatic cancer.