Challenges in the Development of NK-92 Cells as an Effective Universal Off-the-Shelf Cellular Therapeutic.

The human-derived NK-92 cell-based CAR-NK therapy exhibits inconsistency with overall suboptimal efficacy and rapid in vivo clearance of CAR-NK92 cells in cancer patients. Analysis indicates that although pre-existing IgM in healthy individuals (n = 10) strongly recognizes both NK-92 and CAR-NK92 cells, IgG and IgE do not. However, only a subset of cancer patients (3/8) exhibit strong IgM recognition of these cells, with some (2/8) showing pre-existing IgG recognition.

Nanobody Library Construction by Using Gene Designated-Region Pan-Editing Technology.

Camelid single-domain antibody fragments (nanobodies) are an emerging force in therapeutic biopharmaceuticals and clinical diagnostic reagents in recent years. Nearly all nanobodies available to date have been obtained by animal immunization, a bottleneck restricting the large-scale application of nanobodies. In this study, we developed three kinds of gene designated-region pan-editing (GDP) technologies to introduce multiple mutations in complementarity-determining regions (CDRs) of nanobodies .

Chimeric antigen receptor-modified macrophages trigger systemic anti-tumour immunity.

Preliminary results and emerging data have shown that lipid droplet high (LD ) immunosuppressive cells accumulate in tumour tissues. By tracking and phenotypic profiling of LD cells, we find that LD CD19 , LD CD11b , and LD Ly6G immune cell populations appear in the spleen, thymus, and tumour tissues in a syngeneic tumour model. Using a contact-dependent reporter system, we discover a LD CCR7 immunosuppressive cell population that migrates from tumour tissues to the spleen and thymus.