We show here that CD33 knockout (KO) HSPC can generate functional hematopoiesis that is resistant to CD33-targeted AML therapy in two relevant preclinical models and provide evidence for the clinical feasibility and efficacy of combining allogeneic transplantation of CD33 KO HSPCs with CD33 CAR T therapy to treat patients with otherwise ...

2024年9月30日 · We generate CD33-specific, AML-targeted CAR-NK cells (CAR33) combined with CRISPR/Cas9-based gene disruption of the NKG2A-encoding KLRC1 gene. Using single-cell multi-omics analyses, we...

2018年5月31日 · Autologous CD33 KO HSPC transplantation in rhesus macaques demonstrated long-term multilineage engraftment of gene-edited cells with normal myeloid function. CD33-deficient cells were impervious to CD33-targeting CAR T cells, allowing for efficient elimination of leukemia without myelotoxicity.

We show here that CD33 knockout (KO) HSPC can generate functional hematopoiesis that is resistant to CD33-targeted AML therapy in two relevant preclinical models and provide evidence for the clinical feasibility and efficacy of combining allogeneic transplantation of CD33 KO HSPC with CD33 CAR T therapy to treat patients with otherwise ...

2024年9月30日 · We generate CD33-specific, AML-targeted CAR-NK cells (CAR33) combined with CRISPR/Cas9-based gene disruption of the NKG2A-encoding KLRC1 gene. Using single-cell multi-omics analyses, we identified transcriptional features of activation and maturation in CAR33-KLRC1 ko -NK cells, which are preserved following exposure to AML cells.

2024年9月19日 · Current CD33-targeted immunotherapies typically recognize the membrane-distal V-set domain of CD33. Here, we show that decreasing the distance between T cell and leukemia cell membrane increases the efficacy of CD33 chimeric antigen receptor (CAR) T cells.

2019年5月1日 · IVT gRNA demonstrated better knock-out (KO) efficiency than both synRNAs (CD33 surface expression baseline 97.65%; IVT gRNA 0.87-1.33%; synRNA-1 2.15-2.25%, synRNA-2 5.76-7.36%). Two different electroporation settings showed similar CD33 KO efficiency.

2023年12月14日 · CD33-KO cells were diluted with unedited cells to generate an editing titration curve from 10% to 90% editing frequency, with 90% being CD33-KO cells alone. Following 9 days of in vitro myeloid differentiation to monocytes, CD33 surface protein expression (flow cytometry) was correlated with CD33 editing frequency (ICE) (left panel).

2021年11月11日 · The human CD33-positive myeloid cell line MV4-11 was used to test the knockout (KO) efficiency of the six gRNAs resulting in functional loss of CD33. Lentiviruses carrying Cas9, gRNA and GFP genes were used to transduce target cells.

Autologous CD33 KO HSPC transplan-tation in rhesus macaques demonstrated long-term multilineage engraftment of gene-edited cells with normal myeloid function. CD33-deficient cells were impervious to CD33-targeting CAR T cells, allowing for efficient elimination of leukemia without myelo-toxicity.