LB-100

P1/2, N=21, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Jan 2025 --> Jan 2026 | Trial primary completion date: Jan 2025 --> Jan 2026

P1/2, N=21, Recruiting, M.D. Anderson Cancer Center | Not yet recruiting --> Recruiting | Initiation date: Mar 2024 --> Nov 2023

P1, N=43, Not yet recruiting, The Netherlands Cancer Institute

P1/2, N=21, Not yet recruiting, M.D. Anderson Cancer Center

P1, N=37, Not yet recruiting, The Netherlands Cancer Institute

P2, N=7, Completed, National Cancer Institute (NCI) | Recruiting --> Completed | N=25 --> 7 | Trial completion date: Aug 2023 --> Aug 2022 | Trial primary completion date: Aug 2023 --> Aug 2022

P1/2, N=152, Recruiting, Grupo Espanol de Investigacion en Sarcomas | Not yet recruiting --> Recruiting

In conclusion, B7-H3 was found to be upregulated in malignant meningiomas. The PP2A inhibitor LB-100 increased the phosphorylation of STAT1 and B7-H3 expression, which could increase the sensitivity of malignant meningiomas to B7-H3 targeted immunotherapy.

Our findings indicate that PP2A may serve as a potential therapeutic target in BLCA through regulating p21 stability.

Moreover, LB-100 pretreatment partially restored nab-PTX sensitivity in the resistant cell lines and synergistically inhibited the tumor growth of nab-PTX resistant xenografts with nab-PTX. In summary, our study identifies a novel mechanism whereby elevated PP2A activity stabilizes MCL1 protein, increases OXPHOS, and confers nab-PTX resistance, suggesting that targeting PP2A is a potential strategy for reversing nab-PTX resistance in patients with advanced ESCC.

Collectively, PDCD10 promotes EMT and the progression of HCC by interacting with PP2Ac to promote YAP activation, which provides new insight into the mechanism of cancer metastasis. PDCD10 may be a potential prognostic biomarker and therapeutic target for HCC.

Overall, combined PRMT5 and PP2A inhibition had significantly greater antitumor effects than PRMT5 inhibition alone.

Our findings suggest FGFR and PP2A signaling as potential new therapeutic targets for the treatment of DIPGs.

This is the first preclinical investigation of the effect of combining PP2A inhibition with PD1 blockade for GBM. This novel combination provided effective tumor immunotherapy and long-term survival in our animal GBM model.

Similarly, inhibition of PP2A using small molecule inhibitor LB100 showed similar effect...PP2A KO lead to lower AKT phosphorylation upon CD28 stimulation, along with lower proliferative capability of CD8+ T cells upon stimulation with anti-CD28 and suboptimal anti-CD3 concentration. Thus this study highlights the potentially important role of PP2A in CD8+ T cells and its therapeutic consideration for designing combinatorial immunotherapy.

We also found that LB-100 sensitizes TNBC cells to clinically used chemotherapeutical agents, including paclitaxel and cisplatin. Importantly, we found that LB-100 effectively inhibits the growth of MDA468 tumors in mice in vivo without apparent toxicity. Collectively, these data suggest that pharmacological inhibition of PP2A activity could be a novel therapeutic strategy for treating patients with TNBC in a clinical setting.

Our studies demonstrate that LB-100 enhanced anti-CAIX CAR-T cell treatment efficacy in vitro and in vivo. Our findings demonstrate the role of LB-100 in augmenting the cytotoxic activity of anti-CAIX CAR-T cells and underscore the synergistic therapeutic potential of applying combination LB-100 and CAR-T Cell therapy to other solid tumors.