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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

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Meeting abstracts


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.


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.


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.