Plant-made immunotoxin building blocks: A roadmap for producing therapeutic antibody-toxin fusions

Knödler, Matthias; Buyel, Johannes F.

doi:10.1016/j.biotechadv.2020.107683

Cited by 23 publications

(23 citation statements)

References 245 publications

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“…In fact, the cell-binding moiety of ricin, the B chain, is a lectin that is able to recognize galactose residues, driving the catalytic active A domain inside virtually every type of cell. For this reason, the B domain was replaced by the corresponding antibody-based targeting moiety in ricin-based ITX [ 32 ]. Similarly, truncated forms of PE of 38kDa or 40kDa (named PE38 and PE40, respectively), deprived of the natural targeting moiety, have been widely used in ITX design [ 13 ].…”

Section: Cytotoxic Non-human Moietiesmentioning

confidence: 99%

Antibody-Based Immunotoxins for Colorectal Cancer Therapy

et al. 2021

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Monoclonal antibodies (mAbs) are included among the treatment options for advanced colorectal cancer (CRC). However, while these mAbs effectively target cancer cells, they may have limited clinical activity. A strategy to improve their therapeutic potential is arming them with a toxic payload. Immunotoxins (ITX) combining the cell-killing ability of a toxin with the specificity of a mAb constitute a promising strategy for CRC therapy. However, several important challenges in optimizing ITX remain, including suboptimal pharmacokinetics and especially the immunogenicity of the toxin moiety. Nonetheless, ongoing research is working to solve these limitations and expand CRC patients’ therapeutic armory. In this review, we provide a comprehensive overview of targets and toxins employed in the design of ITX for CRC and highlight a wide selection of ITX tested in CRC patients as well as preclinical candidates.

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Section: Cytotoxic Non-human Moietiesmentioning

confidence: 99%

Antibody-Based Immunotoxins for Colorectal Cancer Therapy

et al. 2021

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“…Usually, lower effects may affect low efficacy, so there may be a trade-off. Therefore, there is a need to develop targeted therapy that uses super toxic plant-derived toxins as warheads that are to be conjugated to monoclonal antibodies targeting the CRC-specific antigens [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Current Status, Distribution, and Future Directions of Natural Products against Colorectal Cancer in Indonesia: A Systematic Review

et al. 2021

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In 2020, an estimated 19.3 million new cancer cases and nearly 10 million cancer deaths have occurred worldwide, with colorectal cancer ranking as the third most frequently diagnosed (10.0%). Several attempts have been conducted against cancer, including surgery, radiation, monoclonal antibodies, and chemotherapy. Many people choose natural products as alternatives against cancer. These products will not only help in human life preservation but also work as a source of up-to-date information, leading people away from incorrect information. We discuss the current status, distribution, and future implications of protecting populations with natural products as an alternative against colorectal cancer in Indonesia. Thirty-eight studies were included in this review for data extraction. The distribution of natural products in Indonesia that have potential activity against colorectal cancer cells was predominated by terpenoids, followed by phytosterols, phenolics, alkaloids, and polyisoprenoids. The type of cell line utilized in the cytotoxic activity analysis of natural products was the WiDr cell line, followed by HT-29 cells and HCT-116 cells. This review showed that MTT in vitro assay is a general method used to analyze the cytotoxic activity of a natural product against colorectal cancer cells, followed by other in vitro and in vivo methods. The systematic review provided predictions for several secondary metabolites to be utilized as an alternative treatment against colorectal cancer in Indonesia. It also might be a candidate for a future co-chemotherapy agent in safety, quality, and standardization. In addition, computational methods are being developed to predict the drug-likeness of compounds, thus, drug discovery is already on the road towards electronic research and development.

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“…Third, plants are almost free of endotoxins such as lipopolysaccharides, which are abundant in bacterial cells. Further, the conditions for plant growth are much less affected by microorganisms that are detrimental to mammalian cell cultures (Buyel et al, 2017 ; Moon et al, 2019 ; Muthamilselvan et al, 2019 ; Knodler and Buyel, 2021 ; Schillberg and Finnern, 2021 ). In addition, previous studies indicated that various useful proteins of different origins, such as bacteria, bacteriophage, animals, and red algae, remained functional when produced in tobacco ( Nicotiana benthamiana ) (Garvey et al, 2013 ; Islam et al, 2019 , 2020 ; Kumari et al, 2020 ; Razzak et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Production of Gloeophyllum trabeum Endoglucanase Cel12A in Nicotiana benthamiana for Cellulose Degradation

et al. 2021

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Lignocellulosic biomass from plants has been used as a biofuel source and the potent acidic endoglucanase GtCel12A has been isolated from Gloeophyllum trabeum, a filamentous fungus. In this study, we established a plant-based platform for the production of active GtCel12A fused to family 3 cellulose-binding module (CBM3). We used the signal sequence of binding immunoglobulin protein (BiP) and the endoplasmic reticulum (ER) retention signal for the accumulation of the produced GtCel12A in the ER. To achieve enhanced enzyme expression, we incorporated the M-domain of the human receptor-type tyrosine-protein phosphatase C into the construct. In addition, to enable the removal of N-terminal domains that are not necessary after protein expression, we further incorporated the cleavage site of Brachypodium distachyon small ubiquitin-like modifier. The GtCel12A-CBM3 fusion protein produced in the leaves of Nicotiana benthamiana exhibited not only high solubility but also efficient endoglucanase activity on the carboxymethyl cellulose substrate as determined by 3,5-dinitrosalicylic acid assay. The endoglucanase activity of GtCel12A-CBM3 was maintained even when immobilized on microcrystalline cellulose beads. Taken together, these results indicate that GtCel12A endoglucanase produced in plants might be used to provide monomeric sugars from lignocellulosic biomass for bioethanol production.

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Plant-made immunotoxin building blocks: A roadmap for producing therapeutic antibody-toxin fusions

Cited by 23 publications

References 245 publications

Antibody-Based Immunotoxins for Colorectal Cancer Therapy

Antibody-Based Immunotoxins for Colorectal Cancer Therapy

Current Status, Distribution, and Future Directions of Natural Products against Colorectal Cancer in Indonesia: A Systematic Review

Production of Gloeophyllum trabeum Endoglucanase Cel12A in Nicotiana benthamiana for Cellulose Degradation

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