The development of recombinant immunotoxins (RITs) as a novel therapeutic strategy has made a
revolution in the treatment of cancer. RITs result from the fusion of antibodies to toxin proteins for targeting
and eliminating cancerous cells by inhibiting protein synthesis. Despite indisputable outcomes of RITs regarding
inhibition of multiple cancer types, high immunogenicity has been known as the main obstacle in the clinical
use of RITs. Various strategies have been proposed to overcome these limitations, including immunosuppressive
therapy, humanization of the antibody fragment moiety, generation of immunotoxins originated from
endogenous human cytotoxic enzymes, and modification of the toxin moiety to escape the immune system.
This paper is devoted to review recent advances in the design of immunotoxins with lower immunogenicity.
Keywords: Recombinant immunotoxin, toxins, immunogenicity, immunosuppressive therapy, anti-drug antibodies, humanization, fragment.
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