Toll 样受体 (TLR) 是一类模式识别受体 (PRR)，对于检测感染和激活导致促炎细胞因子和干扰素产生的下游信号通路至关重要。 TLR 途径是一种有吸引力的、积极研究的靶途径。由于其强大的免疫刺激活性，TLR 被认为是全身治疗的“双刃剑”，甚至在癌症领域也是如此。为了解决这个问题，我们开发了基于葡聚糖的 TAM 靶向激活结合物 (D-TAC) 技术，该技术成功地利用肿瘤相关巨噬细胞 (TAM) 来递送 TLR7 激动剂 DSP-0509。我们使用低分子量右旋糖酐靶向 CD206 高 M2 型巨噬细胞，激活它们，并诱导表型转变为抗肿瘤 M1 型巨噬细胞，从体内快速清除并具有惊人的抗肿瘤活性。我们还证明，我们的最佳候选药物 5DEX-0509R 的抗肿瘤作用取决于 TAM 的丰度，这与其作用机制一致。我们相信，通过D-TAC技术产生的5DEX-0509R可以成为临床适用的针对TLR信号通路的免疫疗法。

Toll-like receptors (TLRs) are a class of pattern recognition receptors (PRRs) crucial for the detection of infections and activation of downstream signaling pathways that lead to the production of pro-inflammatory cytokines and interferons. The TLR pathway is an attractive actively studied target pathway. Because of their strong immunostimulatory activity, TLRs are thought to be a "double-edged sword" for systemic treatment, even in the cancer field. To solve this, we have developed dextran-based TAM targeting activating conjugate (D-TAC) technology, which successfully uses tumor-associated macrophages (TAMs) to deliver the TLR7 agonist DSP-0509. We used low molecular weight dextran to target CD206 high M2-type macrophages, activate them, and induce a change in phenotype to antitumor M1-type macrophages with rapid clearance from the body and astonishing antitumor activity. We also demonstrated that the antitumor effect of our best drug candidate 5DEX-0509R is dependent on the abundance of TAMs, which is consistent with their mechanism of action. We believe that 5DEX-0509R generated by D-TAC technology can be a clinically applicable immunotherapy targeting the TLR signaling pathway.