Journal
JOURNAL OF DRUG TARGETING
Volume 29, Issue 8, Pages 848-862Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/1061186X.2021.1894435
Keywords
Immunotoxin; nanobody; single-domain antibody; variable fragment of heavy-chain only antibody; Pseudomonas exotoxin A; diphtheria toxin; ribosome-inactivating proteins
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Immunotoxins (ITs) are protein-based drugs composed of targeting and cytotoxic moieties, successful in treating hematologic malignancies. The use of nanobodies (Nbs) as a targeting moiety may help overcome the poor penetration of ITs into solid tumors.
Immunotoxins (ITs) are protein-based drugs that compose of targeting and cytotoxic moieties. After binding the IT to the specific cell-surface antigen, the IT internalises into the target cell and kills it. Targeting and cytotoxic moieties usually include monoclonal antibodies and protein toxins with bacterial or plant origin, respectively. ITs have been successful in haematologic malignancies treatment. However, ITs penetrate poorly into solid tumours because of their large size. Use of camelid antibody fragments known as nanobodies (Nbs) as a targeting moiety may overcome this problem. Nbs are the smallest fragment of antibodies with excellent tumour tissue penetration. The ability to recognise cryptic (immuno-evasive) target antigens, low immunogenicity, and high-affinity are other fundamental characteristics of Nbs that make them suitable candidates in targeted therapy. Here, we reviewed and discussed the structure and function of ITs, Nbs, and nanobody-based ITs. To gain sound insight into the issue at hand, we focussed on nanobody-based ITs.
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