Chimeric antigen receptor T cell (CAR-T) otherwise known as engineering T cell immunotherapy and T cell receptor T cell (TCR-T) has emerged as a viable therapeutic strategy for treating tumors.
The genetic manipulation of primary T cell, however, remains inefficient, particularly during the clinical manufacturing process. Urgent needs have arisen to develop a reliable technique for the preparation of engineered T cells.
At the Shenzhen Institutes of Advanced Technology (SIAT) of the Chinese Academy of Sciences, a team of researchers led by Prof. CAI Lintao as well as other collaborators have developed a 'safe efficient and universal' technique based on bioorthogonal chemistry and glycol-metabolic labeling for viral-mediated engineered T cell manufacturing. These researchers published their discoveries in Advanced Functional Materials.
The researchers attached the functional azide motifs on T cell surfaces, for this approach, via the intrinsic glycometabolism of exogenous azide-glucose, thereby serving as an artificial ligand for viral binding. They also coated the complementary functional moiety dienzocyclooctyne (DBCO)/-conjugated PEI1.8K (PEI-DBCO) on the lentiviral surface, which strengthened the virus-T cell interaction through DBCO/azide bioorthogonal chemistry.
CAI said that they discovered that this artificial chemical receptor effectively facilitated viral bindings to T cells and elevated the transduction efficiency of the lentivirus from 20 percent to 80 percent without any effect on T cell proliferation activity. The alteration on this artificial chemical was also suitable for launching other heterologous genes into T cells, including GPF, CAR, and TCR, indicating an excellent potency for universal T cell engineering.
The demonstration on the technique confirmed it to be safe for human primary T cells as well, without interference from cell expansion or antitumor functions. When the scientists place it into the CAR-T preparation, the PEI-DBCO/azide-glucose system considerably increased the yield of CAR T cells and boosted their antitumor effect both in vitro and in the B lymphoma xenograft mouse model with a small amount of CAR-T cells, consequently reducing clinical adverse effects.
CAI stated that the labeling strategy of the artificial chemical is a secure, safe, and effective upgrade for viral-based gene manipulation of human primary T cells, thus showing great potential for clinical engineered T lymphocyte manufacturing, including CAR-T and TCR-T cell therapy.
The corresponding author of the paper, Prof. CAI was selected as a Fellow of the American Institute for Medical and Biological Engineering (AIMBE) on March 25 at the American Academy of Sciences in Washington, a nonprofit institute established in 1991, for his involvements relating optical probes and biomimetic drug delivery systems in the fields of nanomedicine and cancer theranostics.
