AUNP-12

Additionally, pre-treatment gene expression of TAM receptors and PD-L1 were significantly higher in major responders compared to the non-responders, in animals that received sitravatinib and AUNP-12 (P < 0.02), confirming that TAM suppression enhances the efficacy of PD-1 blockade. In conclusion, this study proposes a promising immunomodulatory strategy using a multi-gene TKI to overcome developed resistance to an ICI in EAC, establishing rationale for future clinical development.

[ Ga]Ga-AUNP-12 was successfully developed as a PD-L1-specific PET imaging tracer in preclinical and first-in-human studies.

Herein, a kind of tumor cascade-targeted responsive liposome (NLG919@Lip-pep1) is developed by conjugating polypeptide inhibitor of PD-1 signal pathway (AUNP-12), which is also a targeted peptide that conjugated with liposome carrier through matrix metalloproteinase-2 (MMP-2) cleavable peptide (GPLGVRGD). The exposure of secondary targeting module II VRGDC-NLG919@Lip mediated tumor cells targeting, and further relieved the immunosuppressive microenvironment. Overall, this study offers a potentially appealing paradigm of a high efficiency, low toxicity, and simple intelligent responsive drug delivery system for targeted drug delivery in breast cancer, which can effectively rescue and activate the body's anti-tumor immune response and furthermore achieve effective treatment of metastatic breast cancer.

Here, we showed limited toxicity with significant tumor shrinkage in pexidartinib treated animals compared to controls, single agent and in combination with a PD-1 inhibitor, AUNP-12. Moreover, a post-treatment serum cytokine assay exhibited similar systemic trends as the gene expression in the TME, depicting increases in pro-inflammatory cytokines and decreases in anti-inflammatory cytokines. In conclusion, our study established a promising combinatorial strategy using a CSF-1R inhibitor to overcome resistance to PD-1/PD-L1 axis blockade in an EAC model, providing the rationale for future clinical strategies.

Its photothermal therapy can promote the infiltration of T lymphocytes in addition to ablating tumor cells and AUNP-12 and PQ912 further boost both the innate and adaptive immune reactions by cutting off PD-L1 and CD47 signals, respectively. In contrast to earlier single immunotherapy, the nanocomposites exhibit a stronger anti-tumor immune effect without obvious autoimmune side effects, promoting infiltration of T lymphocyte into the tumor site and strengthening phagocytosis of macrophages, even more exciting, significantly reversing pro-tumor M2-like tumor-associated macrophages (TAMs) to anti-tumor M1-like TAMs. The research may provide a promising strategy to develop high-efficient and low-toxic immunotherapy based on nanotechnology.