No abstract

Background.Case. Conclusion.JJLC.

Background. Case. Conclusion.JJLC.

Background. Case. Conclusion.

CD8 + T cells, dendritic cells and macrophages were increased in 4 of 6 patients post LMB-100 treatments. The enhanced anti-tumor effects with LMB-100/aPD1 combination were also observed in the PBMC humanized mouse model transplanted with the tumor cells derived the patient with complete response. In the 531LN2-hMSLN mouse syngeneic model, tumor growth was significantly inhibited by LMB-100/ aPD-1 treatments than either monotherapy and overall survival was improved in the combination treated mice. The median tumor volume was 865mm 3 , 420mm 3 , 277mm 3 , and 65mm 3 in untreated, LMB-100treated, aPD-1-treated, and combination treated groups respectively on day 34 post tumor inoculation (p<0.001). We observed increased expression of genes related to CD8 + T cells and antigen presentation in tumors treated with LMB-100/aPD-1 compared to either agent alone. Flow cytometry confirmed the CD8 + T cells increase in LMB-100 /aPD-1 treated 531LN2-hMSLN tumor. Depletion of CD8 + T cells significantly negated the anti-tumor benefits in LMB-100/aPD-1-treated mice. Conclusion: Pembrolizumab following LMB-100 is associated with durable tumor response in mesothelioma patients as well as pre-clinical models of mesothelioma and lung cancer. This combination is currently being evaluated in a prospective clinical trial in patients with mesothelioma (clinicaltrials.gov # NCT03644550).