:
The development of recombinant immunotoxins (RITs) as a novel therapeutic strategy has made a revolution in
the treatment of cancer. RITs are resulting from the fusion of antibodies to toxin proteins for targeting and eliminating
cancerous cells by inhibiting protein synthesis. Despite indisputable outcomes of RITs regarding inhibiting 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 devoted to reviewing recent advances in the design of immunotoxins with
lower immunogenicity.