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Published on: January 29, 2019
Clinical targeting recombinant immunotoxins for cancer therapy
Meng Li1, Zeng-Shan Liu1, Xi-Lin Liu1
1Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, China-Japan Union Hospital, The First Hospital, Jilin University, Changchun.
Abstract:
Recombinant immunotoxins (RITs) are proteins that contain a toxin fused to an antibody or small molecules and are constructed by the genetic engineering technique. RITs can bind to and be internalized by cells and kill cancerous or non-cancerous cells by inhibiting protein synthesis. A wide variety of RITs have been tested against different cancers in cell culture, xenograft models, and human patients during the past several decades. RITs have shown activity in therapy of several kinds of cancers, but different levels of side effects, mainly related to vascular leak syndrome, were also observed in the treated patients. High immunogenicity of RITs limited their long-term or repeat applications in clinical cases. Recent advances in the design of immunotoxins, such as humanization of antibody fragment, PEGylation, and modification of human B- and T-cell epitopes, are overcoming the above mentioned problems, which predict the use of these immunotoxins as a potential therapeutic method to treat cancer patients.
Insights
Recombinant immunotoxins (RITs) show promise for cancer therapy by targeting and killing cancer cells. Advances in RIT design are overcoming side effects and immunogenicity, paving the way for improved cancer treatments.
Area of Science:
- Biotechnology
- Oncology
- Immunology
Background:
- Recombinant immunotoxins (RITs) are engineered proteins combining toxins with antibodies for targeted cell killing.
- RITs function by binding to cells, internalization, and inhibition of protein synthesis, leading to cell death.
- Historically, RITs have demonstrated anti-cancer activity but faced challenges with side effects and immunogenicity.
Purpose of the Study:
- To review the development and therapeutic potential of recombinant immunotoxins in cancer treatment.
- To highlight recent advancements addressing limitations of earlier RIT designs.
- To assess the future prospects of RITs as a viable cancer therapy.
Main Methods:
- Review of scientific literature on recombinant immunotoxins and their applications in cancer.
- Analysis of RIT mechanisms of action, efficacy, and toxicity.
- Evaluation of recent design modifications aimed at improving RIT performance and safety.
Main Results:
- RITs have shown efficacy against various cancers in preclinical and clinical studies.
- Vascular leak syndrome is a notable side effect associated with RIT therapy.
- High immunogenicity has limited long-term or repeated use of RITs.
Conclusions:
- Recent innovations in RIT design, including antibody humanization and PEGylation, are mitigating side effects and immunogenicity.
- These advancements suggest that immunotoxins hold significant potential as a future therapeutic strategy for cancer patients.
- Further development of RITs could lead to more effective and safer cancer treatments.
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