Gonzalez Norris (mallmoon5)

Recurrence and progression of non-muscle-invasive bladder cancer (NMIBC), frequent despite the availability of multiple treatment modalities, may be partly explained by the presence of immunosuppressive cell populations. We hypothesized that progression of disease could be prevented by the administration of an activated T cell immunotherapy (ACT) at time points when immunosuppressive populations increased in peripheral blood. In an N-of-1 study, a patient with multiple primary bladder high grade urothelial carcinomas, previously treated with standard local resection and chemotherapy but with evidence of progression, received ACT consisting of dendritic cells mixed with cytokine induced killer cells (DC/CIK), intravenously 18 times over a 6 year period at indicated time of observed increases in peripheral blood immunosuppressive CD8+/CD28- cells. Peripheral blood was analyzed for T cell phenotype by flow cytometry, T cell receptor (TCR) repertoire, and circulating tumor DNA (ctDNA) by next generation sequencing (NGS) at the time of each infusion. Cystoscopy and pelvic CT scans were performed at routine intervals to assess clinical status of disease. There has been no recurrence or metastasis of urothelial carcinoma. Peripheral blood cytotoxic T cells and unique TCR clones increased and suppressive T cell populations decreased after DC/CIK infusions evidenced by the two more proof-of concept cases. ART899 ctDNA analysis detected mutations in six genes (ARID1B, MYCN, CDH23, SETD2, NOTCH4 and FAT1) which appeared at different times, but all of them disappeared after the DC-CIK infusions. These data suggest that DC/CIK infusions may be associated with beneficial changes in T cell phenotype, TCR repertoire, decreases in circulating tumor DNA and sustained recurrence-free survival.CAN017 (AV-203), a novel anti-HER3 antibody, exerts very promising anti-tumor activities in several human tumor models. The aim of this study was to further investigated the efficacy and possible responsive biomarkers of CAN017 in esophageal squamous cell carcinoma (ESCC) with Chinese characteristics. Two separate cohorts of ESCC patient-derived xenograft (PDX) models including 24 (cohort 1 as training models, from Crown Bioscience Inc.) and 22 (cohort 2 as validating models, from Peking University Cancer Hospital) models, respectively, were used to study the efficacy and safety of CAN017, as well as the correlation of NRG1 expression to the response of CAN017. In cohort 1, all PDX models showed good tolerance to CAN017 and 8 out of 24 (33.3%) PDX models responded to CAN017 with tumor growth inhibition (TGI) ≥70% compared to controls. Furthermore, the efficacy of CAN017 was positively correlated with NRG1 expression and the response rates in cohort 1 were 73% (8/11) versus 0% (0/13) in NRG1 high and low expression models, respectively. These results were also validated in PDX models of cohort 2 indicated as the powerful anti-tumor activity of CAN017 in PDX models with NRG1 high expression. In our study, HER3-targeting therapy was first demonstrated to have potency in inhibiting ESCC tumor growth, and NRG1 served as a predictive biomarker to screen patients in future clinical trials.MLL rearrangement is very common in solid tumor therapy-related acute myeloid leukemia (t-AML). To investigated the prognosis of solid tumor MLL t-AML, 157 patients were divided into 3 groups non-MLL t-AML (n=41), MLL t-AML (n=18) and MLL de novo AML (n=98). Of the 150 patients underwent anti-leukemia therapy, the complete remission (CR) was similar in MLL t-AML, non-MLL t-AML and MLL de novo AML (P=0.251). 3-years overall survival (OS) was 37.5%, 21.5% and 20.4% (P=0.046), and leukemia-free survival (LFS) was 28.0%, 32.2% and 22.7% (P=0.031), and the incidence of relapse was 30.0%, 50.4% and 53.5% (P=0.382), respectively, in the three groups. Multivariate analysis revealed that MLL t-AML was a risk factor while allo-HSCT was a protective factor for OS, LFS, and relapse (P le