ALBERT

Description: Sequencing and de novo assembly of a near complete indica rice genome Nature Communications, Published online: 4 May 2017; doi:10.1038/ncomms15324 High-quality reference genomes facilitate analysis of genome structure and variation. Here Du et al . create a near-complete assembly of the indica rice genome by combining single molecule sequencing with mapping data and fosmid sequences and identify genetic variants by comparison with other rice genomes.

Description: Crops carrying broad-spectrum resistance loci provide an effective strategy for controlling infectious disease because these loci typically confer resistance to diverse races of a pathogen or even multiple species of pathogens. Despite their importance, only a few crop broad-spectrum resistance loci have been reported. Here, we report the identification and...

Description: CBMG has developed C-CAR088, a novel chimeric antigen receptor (CAR)-T cell therapy targeting BCMA, which is specifically and highly expressed on multiple myeloma cells. C-CAR088 is designed to improve efficacy through increasing the specificity and reducing immunogenicity by fusing a scFv from high-affinity human monoclonal antibody to a CD3ζ/4-1BB signaling domain. In preclinical study, the human T cells transduced with the lentiviral vector encoding C-CAR088 exhibited specific functions in vitro including CAR-T proliferation, cytokine production, cytotoxicity to BCMA positive tumor cells. C-CAR088 cells were not activated by soluble BCMA protein and MM patient serums. However, they can eradicate BCMA positive tumor cells in vivo including BMCA positive multiple myeloma tumor model RPMI-8226. C-CAR088 is manufactured in a serum free, automated and digital, closed system which produce CAR-T cells with stable and high percentage of Tcm phenotype. C-CAR088 showed a very good dose dependent tumor inhibition effect and survival benefit in animal studies. A Phase 1, 3+3 dose escalation trial is being conducted in patients with r/r MM (≥ 3 prior lines, having received treatment and proteasome inhibitors (PI) and IMiD or double refractory) to assess the safety and efficacy of C-CAR088 (NCT03815383). Patients are apheresed to harvest T cells. C-CAR088 is then manufactured and administered to patients as a single intravenous dose after a standard 3-day cyclophosphamide/fludarabine conditioning regimen. As of July 5, 2019 cutoff date, 3 patients have been treated with C-CAR088 at the dose of 1.0 x 106 CAR-T cells/kg. Patients were heavily pre-treated (7 prior lines of therapy), and all failed IMiDs and proteasome inhibitor therapies. After C-CAR088 treatment, all three patients showed clinical improvement as early as two weeks post treatment. Furthermore, C-CAR088 proliferation & expansion in the peripheral blood correlated with the decrease of tumor burden. Two patients reached VGPR at 4 weeks and 8 weeks respectively, and the third patient reached PR as early as 2 weeks post C-CAR088 infusion. C-CAR088 treatment was well tolerated, no dose-limiting toxicities (DLTs), reversible Grade 1~2 CRS observed. In conclusion, early clinical trial results in patients with r/r MM for C-CAR088 support preclinical findings that the drug shows promising efficacy and manageable safety profile.The very early clinical efficacy signal at low, suboptimal dose is encouraging and compares favorably to many other anti-BCMA CAR-T products at similar dose. The promising trend needs to be confirmed by the ongoing clinical trial. Disclosures Yao: Cellular Biomedicine Group Inc: Employment, Equity Ownership. Zhu:Cellular Biomedicine Group Inc: Employment, Equity Ownership. Huang:Cellular Biomedicine Group Inc: Employment, Equity Ownership. Zhu:Cellular Biomedicine Group Inc: Employment, Equity Ownership. Wei:Cellular Biomedicine Group Inc: Employment, Equity Ownership. Lan:Cellular Biomedicine Group Inc: Employment, Equity Ownership. LV:Cellular Biomedicine Group Inc: Employment, Equity Ownership. Wu:Cellular Biomedicine Group Inc: Employment, Equity Ownership. Wang:Cellular Biomedicine Group Inc: Employment, Equity Ownership. Yang:Cellular Biomedicine Group Inc: Employment, Equity Ownership. Zheng:Cellular Biomedicine Group Inc: Employment, Equity Ownership. Zhao:Cellular Biomedicine Group Inc: Employment, Equity Ownership. Zhang:Cellular Biomedicine Group Inc: Employment, Equity Ownership. Chen:Cellular Biomedicine Group Inc: Employment, Equity Ownership. Li:Cellular Biomedicine Group Inc: Employment, Equity Ownership. Ren:Cellular Biomedicine Group Inc: Employment, Equity Ownership. Zhang:Cellular Biomedicine Group Inc: Employment, Equity Ownership. Humphries:Cellular Biomedicine Group Inc: Employment, Equity Ownership. Yao:Cellular Biomedicine Group Inc: Employment, Equity Ownership.

Description: Background: C-CAR088, an anti-BCMA CAR T-cell therapy is a novel 2nd generation 4-1BB chimeric antigen receptor T (CAR-T) cell therapy targeting BCMA which is specifically and highly expressed on multiple myeloma (MM) cells. C-CAR088 is manufactured in a serum-free, automated and digital, closed system. Initial, early clinical trial results in patients with R/R MM supported preclinical findings and showed promising efficacy and manageable safety profile (Yao, Blood (2019) 134 (Supplement_1): 50.) Methods: The dose escalation and expansion studies have been conducted at four medical centers in China to evaluate the safety and efficacy of C-CAR088 in patients with R/R MM who were previously treated with at least 2 lines of therapy including proteasome inhibitors (PIs) and IMiDs. C-CAR088 is administered to patients as a single intravenous dose after a standard 3-day cyclophosphamide/fludarabine conditioning regimen. Results: As of July 15, 2020, 24 patients were infused and 21 patients had evaluable data for safety and clinical response at dose levels of 1.0 x 106 CAR-T cells/kg (n=3), 3 x106 CAR-T cells/kg (n=11) and 4.5~6x106 CAR-T cells/kg (n=7). The median vein to vein time was 16 days. The manufacturing success rate was 100%. The median age of patients dosed was 60 years (range: 45-74 years).The median number of prior lines of therapy was 4 (range: 2-12 prior therapies). There were 17 (81%) patients with at least one and 12 (57.1%) patients with at least two high risk cytogenetic tumor changes. Five patients (23.8%) had bridging therapy. C-CAR088 treatment was well tolerated. 20 of 21 (95%) patients had Grade 1-2 CRS and one patient experienced Grade 3 CRS. Median time to CRS was 6.5 days (range: 1-11 days) and median duration of CRS was 5 days (range: 2-10 days). Four patients (19%) received tocilizumab for CRS treatment. Only one patient experienced a Grade 1 neurotoxicity event. No dose-limiting toxicities were observed and all adverse events were reversible. The best overall response (BOR) included 6 complete responses (CRs), 10 very good partial responses (VGPRs) and 4 partial responses (PRs). Median follow-up was 182 days (range: 30-375 days). The median duration of response has not been reached. In the 3 x106 CAR-T cells/kg dose group, 5/11(45%) patients achieved a CR. The C-CAR088 PK profile in peripheral blood showed a trend of a dose dependent profile. AUC0~28day and Cmax increased and Tmax decreased with dose (P

Description: Background: Relapse due to loss of the CD19 targeted epitope presents a therapeutic challenge of CD19 CAR-T therapy. These patients universally have poor outcomes. CD20 is a proven therapeutic target for B-Cell Non-Hodgkin Lymphomas (B-NHL), supported by previously approved and widely used monoclonal antibody therapy. C-CAR066 is a novel 2nd generation chimeric antigen receptor T (CAR-T) therapy. Preclinical studies suggest that C-CAR066 has superior anti-tumor activity compared to CAR-Ts derived from scFVs of Leu16, Rituximab, and Obinutuzumab, Methods: NCT04036019 is a single arm, single-center, non-randomized phase I clinical trial conducted at Shanghai Tongji Hospital to evaluate the safety and efficacy of C-CAR066 in subjects with r/r B cell lymphoma who were previously treated with anti-CD19 CAR-T therapy. The primary objective of the study is to evaluate incidence and severity of treatment emergent adverse events. The secondary objectives include determining overall response rate (ORR), PFS, and OS. C-CAR066 is manufactured in a serum free, semi-automated, and digitally closed system. C-CAR066 is administered to patients as a single intravenous dose after a standard 3-day cyclophosphamide/fludarabine conditioning regimen. Results: As of Aug 3, 2020, 7 patients (all DLBCL) were enrolled and infused with C-CAR066 with a dose range of 2.0 x 106 to 5.0 x 106 CAR-T cells. The manufacturing success rate was 100%. All patients had relapsed after anti-CD19 CAR-T treatment, only one of the patients had achieved CR following anti-CD-19 CAR-T therapy. C-CAR066 treatment was well tolerated with reversible grade 1~2 CRS in six patients, grade 3 CRS in another patient, and no neurotoxicity events. 6/7 patients showed clinical improvement (best overall response rate, BOR = 85.7%). The best overall responses include 3 CR and 3PR. All patients responded to C-CAR066 treatment and showed different degrees of tumor regression (45-100%). Furthermore, the expansion and proliferation of C-CAR066 CAR-T cells in the peripheral blood positively correlated with the extent of tumor regression. Conclusion: C-CAR066 has a favorable safety profile and shows promising early efficacy in patients with r/r NHL following CD19 CAR-T therapy. It confirms that C-CAR066 has a different mechanism of action compared to anti-CD-19 CAR-T therapy. These data provide strong scientific rationale to the strategy of targeting both CD20 and CD19 tumor antigens and to ask whether this leads to superior clinical benefit to targeting either CD19 or CD20 alone in NHL. Disclosures Huang: Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Zhu:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Yao:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Zhu:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Zheng:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Chen:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Lan:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Chen:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Wei:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Shu:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Ye:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Zhang:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Wang:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Hong:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Ren:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Zhang:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Humphries:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Yao:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.

Description: Background: Aiming to improve both the response rate and durability of response while limiting antigen escape of CD-19 following anti-CD-19 CAR-T therapy, C-CAR039 has been developed as a 2nd generation 4-1BB novel bi-specific chimeric antigen receptor T (CAR-T) therapy targeting both CD19 and CD20 antigens. Methods: NCT04317885 is a single arm, single-center, non-randomized phase I clinical trial designed to evaluate the safety and efficacy of C-CAR039 in treatment of relapsed or refractory NHL (r/r NHL) patients. The primary objective of the study is to evaluate incidence and severity of treatment emergent adverse events. The secondary objectives include determining overall response rate (ORR), progression-free survival, and overall survival. Results: In preclinical studies, human T cells transduced with the lentiviral vector encoding C-CAR039in vitroshowed CAR-T proliferation, cytokine production, cytotoxicity to CD19, and CD20 single positive and double positive tumor cells. C-CAR039 can eradicate CD19/CD20 positive tumor cellsin vivobased on our animal model study. A Phase 1 trial was conducted in Shanghai Tongji Hospital in patients with r/r NHL to assess the safety and efficacy of C-CAR039 (NCT04317885). Following apheresis to harvest T cells, C-CAR039 was manufactured and infused as a single intravenous dose after a standard 3-day cyclophosphamide/fludarabine conditioning regimen. C-CAR039 was manufactured in a serum free, semi-automated, and digitally closed system with median vein to vein time of 18 days. The manufacturing success rate was 100%. As of Aug 3, 2020, 16 patients were infused with C-CAR039 with a dose range of 1.0 x 106 to 5.0 x 106 CAR-T cells/kg. 14 patients had at least one-month evaluable safety data and 13 patients (11 DLBCL, 2 FL patients) had one-month or longer efficacy data. C-CAR039 treatment was well tolerated with no grade 3 or higher cytokine release syndrome(CRS) and no neurotoxicity event. Reversible grade 1~2 CRS was observed in 12 (86%) of patients. Cytopenias due to the conditioning regimen were common and reversible. At the one-month evaluation, 12/13 patients showed clinical improvement (ORR=92%) and 11/11 of DLBCL patients responded to the treatment (ORR=100%). Median follow-up was 70 days (range: 35-257 days). The best overall response (BOR) includes 10 complete responses (CRs) and 2 partial responses (PRs). Furthermore, C-CAR039 proliferation and expansion in the peripheral blood positively correlated with tumor regression. Conclusion: C-CAR039 shows promising efficacy and a favorable safety profile in the early clinical trial in patients with r/r NHL. The early clinical efficacy signal is encouraging and compares favorably to anti-CD19 CAR-T therapies. These findings need to be evaluated in more patients with longer follow-up to confirm safety, efficacy and duration of response. Disclosures Huang: Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Zhu:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Yao:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Zhu:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Zheng:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Chen:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Li:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Lan:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Chen:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Guo:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Zhang:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Zheng:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Wang:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Hong:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Ren:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Zhang:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Humphries:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.Yao:Cellular Biomedicine Group Inc:Current Employment, Current equity holder in publicly-traded company.