01718nas a2200181 4500000000100000008004100001100001500042700001300057700001200070700001100082700001500093245019700108856008100305300001200386490000600398520111800404022001401522 2015 d1 aBanerjee S1 aHalder K1 aGhosh S1 aBose A1 aMajumdar S00aThe combination of a novel immunomodulator with a regulatory T cell suppressing antibody (DTA-1) regress advanced stage B16F10 solid tumor by repolarizing tumor associated macrophages in situ. uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4404885/pdf/koni-04-e995559.pdf ae9955590 v43 a

Tumor associated macrophages and tumor infiltrating regulatory T cells greatly hamper host-protective antitumor responses. Therefore, we utilized a novel immunomodulator, heat-killed Mycobacterium indicus pranii (Mw), to repolarize TAM and an agonistic GITR antibody (DTA-1) to reduce intratumoral regulatory T cell frequency for generation of a host-protective antitumor response. Although, the combination of Mw and DTA-1was found to be effective against advanced stage tumors, however, Mw or DTA-1 failed to do so when administered individually. The presence of high level of regulatory T cells abrogated the only Mw induced antitumor functions, whereas only DTA-1 treatment was found to be ineffective due to its inability to induce TAM repolarization in vivo. The combination therapy was found to be effective since DTA-1 treatment reduced the frequency of regulatory T cells to such an extent where they could not attenuate Mw induced TAM repolarization in vivo. Therefore, the combination therapy involving Mw and DTA-1 may be utilized to the success of advanced stage solid tumor immunotherapies.

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