Panoply™ Human CD22 Over-expressing Stable Cell Line

Here, researchers explored a new treatment strategy for relapsed/refractory (R/R) Burkitt lymphoma (BL), namely autologous hematopoietic stem cell transplantation (ASCT) combined with tandem anti-CD19/CD22 chimeric antigen receptor (CAR) T-cell therapy. A 20-year-old Asian male patient had refractory BL, and his lymphoma was unresponsive to multiple chemoimmunotherapy. The patient underwent myeloablative ASCT, and three days later, he was infused with a novel third-generation CAR-T cell, which was modified with CD28 and CD3ζ signaling domains and TLR2 co-stimulatory domains. The therapy achieved sustained complete remission without any serious complications during the 306-day follow-up. This case suggests that myeloablative ASCT combined with tandem anti-CD19/CD22 CAR-T cell therapy may be an effective method for the treatment of R/R BL, which deserves further clinical validation.

The researchers developed a novel tandem CAR-T cell, named 192228zT2. This CAR-T cell integrates a humanized single-chain variable region (scFv) targeting CD19 and CD22 extracellularly, and integrates the CD28 co-stimulatory domain, the Toll-like receptor 2 intracellular domain (11-13) known to enhance the anti-tumor efficacy and migration ability of CAR-T cells, and the CD3ζ motif intracellularly. The lentiviral vector encoding the 192228zT2 CAR-T cells was used for transduction, and the transduction efficiency was measured by protein L staining (Figure 1A). The CAR-T cells were expanded in the presence of recombinant human IL-2 and harvested when the cell number reached the dose requirement. In vitro killing assays showed that 192228zT2 T cells could effectively lyse CD19-overexpressing K562 cells (K562-CD19GL) and CD22-overexpressing K562 cells (K562-CD22GL) (Figure 1B, C), indicating that both anti-CD19 and anti-CD22 single-chain variable fragments (scFv) had killing effects. In addition, 192228zT2 T cells could also effectively kill NALM6-GL, a human B-cell acute lymphoblastic leukemia (B-ALL) cell line that expresses both CD19 and CD22 (Figure 1D).

Figure 1. (A) Transduction efficiency of 1922zT2 T cells. (B-D) In vitro cytotoxic activity of 1922zT2 T cells and mock T cells against CD19+ K562-CD19GL (B), CD22+ K562-CD22GL (C), and CD19+CD22+ NALM6-GL (D) target cells. (Luo X, et al., 2024)