Wang Jianxiang

Disulfide-stabilized diabody antiCD19/antiCD3 exceeds its parental antibody in tumor-targeting activity

BackgroundA diabody is a bispecific antibody that is capable of recruiting a polyclonal T cell to antibody target-expressing tumor cells. However, the two chains of diabodies tend to dissociate because they are integrated non-covalently. Therefore, it is necessary to remodel the diabody to increase its stability in order to enhance the antitumor activity.MethodsWe constructed an antiCD3×antiCD19 diabody with one binding site for the T cell antigen receptor (TCRCD3) and the other for the B cell-specific antigen (CD19) by recombinant gene engineering technology. Cysteine residues were introduced into the V domains of the anti-CD3 segment. The stability and cytotoxicity of the two diabodies were compared in vitro and vivo.ResultsThe disulfide-stabilized (ds) diabodies produced by Escherichia coli were secreted with high yields in a fully active form without a decrease in affinity. Compared with the parental diabody, the disulfide-stabilized (ds) diabody proved more stable in vitro and in vivo without reducing binding affinity. Both were able to effectively eliminate human lymphoma Raji cells by redirecting T lymphocytes in vitro and in vivo, but the ds diabody was more effective in inhibiting the growth of xenografts transplanted in BALB/C nude mice.ConclusionThe antiCD3×antiCD19 ds diabody is more suitable for a controlled polyclonal T cell therapy of human CD19-positive B cell malignancies than its parental diabody.

Ribosome–Lamella Complex Precursors in Acute Monocytic Leukemia: A Study of 6 Cases

The ribosome–lamella complex (RLC) is a cylindrical structure composed of annular lamella associated particles, regarded as ribosomes, around a central core, which is best known in hairy cell leukemia. RLC has been presumed to originate from aggregating rER and ribosomes. Incomplete and maturing RLC structures have been called RLC precursors (pre-RLC). The present paper investigates the various architectural aspects of pre-RLC and the ultrastructural characteristics of the blasts in 6 cases of acute monocytic leukemia (M5) in which these structures occur. Blasts bearing pre-RLC contained irregular nuclei with less heterochromatin and a prominent nucleolus, and many cytoplasmic organelles in an abundant cytoplasm. The findings indicate that pre-RLC might result from an asymmetrical differentiation of organelles in blasts associated with expression of CD117 and CD56 but default of CD14 in M5.

Recent advances in immunotherapy of acute leukemia via chimeric antigen receptor-engineered T cells

Chimeric antigen receptor-engineered T-cell (CAR-T) therapy is a type of adoptive cellular immunotherapy, in which T cells isolated from patients’ or donors’ peripheral blood mononuclear cells are genetically modified, expanded, and reinfused to patients. CAR-T therapy has resulted in encouraging outcomes in patients with B-cell malignancies and is currently being investigated for the treatment of other hematological malignancies. This review discusses the basic structure of CAR, the evolution of CAR structure, the advances in acute leukemia therapy, and the innovative strategies in CAR design and CAR-T production.