BMS-202

BMS 202, a programmed cell death 1/programmed cell death 1 Ligand 1 (PD-L1) inhibitor, was loaded yielding 2P@Lipo-BMS-NBs-O2, which was found to reduce the expression levels hypoxia-inducible factor-1α and PD-L1, synergistically enhanced the pharmacodynamics of BMS 202, meanwhile, enhanced cytotoxic T-cell infiltration...Further incorporation of a fused cytomembrane (FM) from dendritic and B16F10 cells produced FM-2P@Lipo-BMS-NBs-O2, which exhibited superior heterogeneous tumor growth suppression, reduced stemness gene expression, increased CD8+ T-cell infiltration, and elevated IFN-γ levels in serum. Oxygen-carrying nanovaccine possess the features of oxygen delivery, T cell redirection and FM coating, represents full activation of T-cell function and a potent reduction of tumor stemness, offering a promising strategy for the treatment of highly heterogeneous solid tumors.

Additionally, BMS-202 treatment significantly elevated levels of pro-inflammatory cytokines, including IFN-γ and TNF-α, indicating a robust immune response (P<0.001). These findings suggest that BMS-202 effectively promotes apoptosis and enhances immune responses in lung cancer, underscoring its potential as a therapeutic agent in treating lung carcinogenesis.

Herein, M1 macrophage-derived, CXCR4-overexpressed, and BMS202-loaded extracellular vesicles (BMS@C-M1 EV) were constructed to inhibit postoperative melanoma lung metastasis...Therefore, BMS@C-M1 EV through nebulized inhalation could disrupt PMN formation and eliminate CTCs in the lung, effectively suppressing postoperative melanoma lung metastasis. This therapeutic approach holds great potential for preventing postoperative melanoma lung metastasis.

Combined with BMS-202, we explored suppression of the PD-1/PD-L1 complex and synergistic induction of pyroptosis...The synergistic approach of pyroptosis combined with an enhanced immunotherapy nanoplatform shows promise as an effective HCC immunotherapy strategy, with significant clinical translation potential. Future studies will optimize the platform and conduct clinical trials.

To address these challenges, a nanocomposite hydrogel system (Apa/BPNPs@Gel) is developed by encapsulating PD-L1 inhibitor BMS202 nanoparticles coated with polyvinyl alcohol (BPNPs) into a polyvinyl alcohol/alginate hybrid hydrogel...Initially, the antiangiogenic agent apatinib (Apa) is released to alleviate tumor hypoxia through vascular normalization and enhance PD-L1 suppression, priming the TME for subsequent anti-PD(L)1 therapy...Notably, in preclinical cervical carcinoma models, Apa/BPNPs@Gel mediated combination therapy significantly inhibited tumor growth and prolonged survival by activating tumor-suppressed CD8+ T cells. Hence, this locally administrable hydrogel offers a versatile platform to modulate the immunosuppressive TME and enhance immunotherapeutic outcomes.

Additionally, immune profiling of the tumor tissue using IHC revealed an increased CD8+/FOXP3+ ratio and a reduced CD4+/CD8+ ratio, suggesting an immunomodulatory effect. In conclusion, fucoidan demonstrated the potential to enhance the anti-tumor efficacy of BMS-202 via modulation of the immune TME and downregulating key oncogenic pathways, warranting further investigation into its role in combination with immunotherapy.

By inhibiting mitochondrial function, the antitumor effects of BMS‑202 can be enhanced. Overall, the present study provides information on the potential antitumor mechanisms of BMS‑202 as well as a theoretical basis for its application in melanoma therapy.

Functional validation using the PD-1/PD-L1 inhibitor BMS202 revealed dose-dependent suppression of proliferation and enhanced apoptosis in EBV+Farage cells, with TLR4 emerging as a downstream effector showing EBV-status-dependent regulation. These findings not only link TME-driven PD-1/PD-L1 activation to EBV+DLBCL's poor prognosis but also provide preclinical evidence for PD-1/PD-L1 blockade as a therapeutic strategy.

In conclusion, the therapeutic outcome supports the high-efficiency of radiotherapy based on BMS@Pt2Au4 NPs in hypoxic tumors expressing PD-L1.

Additionally, the ICB inhibitor BMS-202 synergizes with the PD-L1 aptamer-assisted nanoradiosensitizer to block the PD-L1 receptor, promoting T cell activation. Furthermore, this nanoradiosensitizer exhibits exceptional photothermal conversion efficiency, amplifying the ICD effect. The PD-L1-targeted nanoradiosensitizer effectively inhibits primary tumor growth and eliminates distant tumors, underscoring the potential of this strategy in optimizing both radioimmunotherapy and photothermal therapy.

Herein, we synthesized iRGD-modified pH-sensitive liposomal nanoparticles co-encapsulating lenvatinib (Len) and the small molecule PD-1/PD-L1 inhibitor BMS-202 (iRGD-lip@Len/BMS-202) to address issues related to inadequate tumor enrichment and distinct pharmacokinetics of these drugs. Collectively, the combination of Food and Drug Administration (FDA)-approved drugs with iRGD-modified liposomes presents a promising strategy for HCC treatment. Simultaneously, IVIM-MRI provides a non-invasive method to accurately predict the response to this nanodrug.

The compound MolPort-001-742-690 emerged as a promising pH-selective inhibitor, showing a significant affinity for PD-L1 in acidic conditions and lower toxicity compared to known inhibitors like BMS-202 and LP23. A detailed 1000 ns molecular dynamics simulation confirmed the stability of the inhibitor-PD-L1 complex under acidic conditions. This research highlights the potential of using in silico techniques to discover novel pH-selective inhibitors, which, after experimental validation, may enhance the precision and reduce the toxicity of immunotherapies, offering a transformative approach to cancer treatment.