A recombinant affitoxin derived from a HER3 affibody and diphteria-toxin has potent and selective antitumor activity

Nazari, Mahboobeh; Emamzadeh, Rahman; Jahanpanah, Maryam; Yazdani, Elnaz; Radmanesh, Ramin

doi:10.1016/j.ijbiomac.2022.08.150

Cited by 4 publications

(1 citation statement)

References 49 publications

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“…One such agent, Affitoxin-1, is a designed toxin that has a shortened version of diptheria toxin and HER3-binding affibody domains to form an affibody, a genetically modified small molecule that shows affinity for binding to target molecules. Afftoxin-1 induced apoptosis in HER3-expressing cells [ 149 ]. HER3 antisense oligonucleotide, EZN-3920 specifically downregulates the expression of HER3, corresponding to growth inhibition.…”

Section: Targeted Her3 Therapiesmentioning

confidence: 99%

HER3 Alterations in Cancer and Potential Clinical Implications

Kilroy

Park

Feroz

et al. 2022

Cancers

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In recent years, the third member of the HER family, kinase impaired HER3, has become a target of interest in cancer as there is accumulating evidence that HER3 plays a role in tumor growth and progression. This review focuses on HER3 activation in bladder, breast, colorectal, and lung cancer disease progression. HER3 mutations occur at a rate up to ~10% of tumors dependent on the tumor type. With patient tumors routinely sequenced for gene alterations in recent years, we have focused on HER3 mutations in bladder, breast, colon, and lung cancers particularly in response to targeted therapies and the potential to become a resistance mechanism. There are currently several HER3 targeting drugs in the pipeline, possibly improving outcomes for cancer patients with tumors containing HER3 activation and/or alterations.

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Section: Targeted Her3 Therapiesmentioning

confidence: 99%

HER3 Alterations in Cancer and Potential Clinical Implications

Kilroy

Park

Feroz

et al. 2022

Cancers

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Uncovering the role of leucine 59 in Renilla luciferase stability and activity with error-prone PCR: Implications for protein engineering

Fanaei-kahrani,

Emamzadeh,

Nazari

2024

Protein Expression and Purification

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Non-Immunoglobulin Synthetic Binding Proteins for Oncology

David,

Pestov,

Korneenko

et al. 2023

Biochemistry Moscow

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Extensive application of technologies like phage display in screening peptide and protein combinatorial libraries has not only facilitated creation of new recombinant antibodies but has also significantly enriched repertoire of the protein binders that have polypeptide scaffolds without homology to immunoglobulins. These innovative synthetic binding protein (SBP) platforms have grown in number and now encompass monobodies/adnectins, DARPins, lipocalins/anticalins, and a variety of miniproteins such as affibodies and knottins, among others. They serve as versatile modules for developing complex affinity tools that hold promise in both diagnostic and therapeutic settings. An optimal scaffold typically has low molecular weight, minimal immunogenicity, and demonstrates resistance against various challenging conditions, including proteolysis – making it potentially suitable for peroral administration. Retaining functionality under reducing intracellular milieu is also advantageous. However, paramount to its functionality is the scaffold’s ability to tolerate mutations across numerous positions, allowing for the formation of a sufficiently large target binding region. This is achieved through the library construction, screening, and subsequent expression in an appropriate system. Scaffolds that exhibit high thermodynamic stability are especially coveted by the developers of new SBPs. These are steadily making their way into clinical settings, notably as antagonists of oncoproteins in signaling pathways. This review surveys the diverse landscape of SBPs, placing particular emphasis on the inhibitors targeting the oncoprotein KRAS, and highlights groundbreaking opportunities for SBPs in oncology.

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A recombinant affitoxin derived from a HER3 affibody and diphteria-toxin has potent and selective antitumor activity

Cited by 4 publications

References 49 publications

HER3 Alterations in Cancer and Potential Clinical Implications

HER3 Alterations in Cancer and Potential Clinical Implications

Uncovering the role of leucine 59 in Renilla luciferase stability and activity with error-prone PCR: Implications for protein engineering

Non-Immunoglobulin Synthetic Binding Proteins for Oncology

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