Genetically encoded immunophotosensitizer

Serebrovskaya, Ekaterina O.; Stremovsky, Oleg A; Chudakov, Dmitriy M.; Lukyanov, Konstantin A.; Deyev, Sergey M.

doi:10.1134/s1068162011010134

Cited by 3 publications

(2 citation statements)

References 27 publications

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“…It was called "killer red" and is particularly influential in terms of bioconjugation as classical chemical reactions requiring harsh conditions and subsequent purification is completely negated if the PS can be encoded and expressed as a fusion protein. Work by Deyev et al [147,148] produced such photo-immunoconjugates and showed specific photo activity and cell killing in vitro, although at the moment not as potently as traditional chemical conjugates.…”

Section: Issues In Making Adp-drugsmentioning

confidence: 95%

Antibody-Directed Phototherapy (ADP)

et al. 2013

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Photodynamic therapy (PDT) is a clinically-approved but rather under-exploited treatment modality for cancer and pre-cancerous superficial lesions. It utilises a cold laser or LED to activate a photochemical reaction between a light activated drug (photosensitiser-drug) and oxygen to generate cytotoxic oxygen species. These free radical species damage cellular components leading to cell death. Despite its benefits, the complexity, limited potency and side effects of PDT have led to poor general usage. However, the research area is very active with an increasing understanding of PDT-related cell biology, photophysics and significant progress in molecular targeting of disease. Monoclonal antibody therapy is maturing and the next wave of antibody therapies includes antibody-drug conjugates (ADCs), which promise to be more potent and curable. These developments could lift antibody-directed phototherapy (ADP) to success. ADP promises to increase specificity and potency and improve drug pharmacokinetics, thus delivering better PDT drugs whilst retaining its other benefits. Whole antibody conjugates with first generation ADP-drugs displayed problems with aggregation, poor pharmacokinetics and loss of immuno-reactivity. However, these early ADP-drugs still showed improved selectivity and potency. Improved PS-drug chemistry and a variety of conjugation strategies have led to improved ADP-drugs with retained antibody and PS-drug function. More recently, recombinant antibody fragments have been used to deliver ADP-drugs with superior drug loading, more favourable pharmacokinetics, enhanced potency and target cell selectivity. These improvements offer a promise of better quality PDT drugs

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Section: Issues In Making Adp-drugsmentioning

confidence: 95%

Antibody-Directed Phototherapy (ADP)

et al. 2013

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“…This limitation compels researchers to construct novel KillerRed variants with sufficient phototoxicity. Even though, the excessive ROS-induced phototoxicity can also cause problems such as necrosis of healthy tissues around the tumor [ 185 ].…”

Section: Challenges and Future Prospectsmentioning

confidence: 99%

Recombinant immunotoxins development for HER2-based targeted cancer therapies

et al. 2021

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Understanding the molecular mechanisms of cancer biology introduces targeted therapy as a complementary method along with other conventional therapies. Recombinant immunotoxins are tumor specific antibodies that their recognizing fragment is utilized for delivering modified toxins into tumor cells. These molecules have been considered as a targeted strategy in the treatment of human cancers. HER2 tumor biomarker is a transmembrane tyrosine kinase receptor that can be used for targeted therapies in the forms of anti-HER2 monoclonal antibodies, antibody–drug conjugates and immunotoxins. There have been many studies on HER2-based immunotoxins in recent years, however, little progress has been made in the clinical field which demanded more improvements. Here, we summarized the HER2 signaling and it’s targeting using immunotherapeutic agents in human cancers. Then, we specifically reviewed anti-HER2 immunotoxins, and their strengths and drawbacks to highlight their promising clinical impact.

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