Application of nanobody‑based CAR‑T in tumor immunotherapy (Review)

Chimeric antigen receptor (CAR) T cell therapy is a type of cellular immunotherapy showing promising clinical effectiveness and high precision. CAR‑T cells express membrane receptors with high specificity, which enable them to identify certain target antigens generated by cancerous cells. The three primary structural elements of the CAR are the extracellular domain, transmembrane domain and cytoplasmic domain. Nanobodies are a type of antibody fragment derived from the variable domains of camelid heavy chain antibodies (VHH), which are the antigen‑specific binding domains. They have high clinical applicability due to their tiny size, excellent target affinity, adaptable functions and guaranteed stability. Structurally pre‑designed nanobodies were transduced in primary T lymphocytes, forming CAR‑T cells and these have been demonstrated to have inhibitory effects on hematologic malignancy or solid tumor cells/tissues both in vivo and in vitro. At present, a number of novel nanobody‑based modalities can include a single nanobody, a bi‑valent nanobody and multivalent nanobody CAR‑T cells with bispecific and multispecific characteristics, showing promising therapeutic efficacy that is similar to CAR‑T cells modulated with a single‑chain variable fragment. Intriguingly, CAR‑T cells targeting the B‑cell maturation antigen modified using an anti‑B‑cell maturation antigen single nanobody or bivalent nanobody have been shown to exhibit clinical efficacy comparable to scFv‑modulated CAR‑T cells. The application of nanobodies in CAR‑T therapy has been well established from laboratory‑based evidence to clinical application and they have great potential for developing advanced CAR‑T cells for more complex employment.