The promising role of antibody drug conjugate in cancer therapy: Combining targeting ability with cytotoxicity effectively

Li, Wenqian; Guo, Hanfei; Li, Lingyu; Zhang, Yong-Fei; Cui, Jiuwei

doi:10.1002/cam4.4052

Cited by 34 publications

(27 citation statements)

References 195 publications

(275 reference statements)

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“…These responses are mediated by the unique features of the conserved Fc antibody domain. These mAbs are intensively investigated as targeting moieties for the vehiculation of cytotoxic drugs, theranostic compounds, and nanoparticles to the tumor microenvironment, with nine conjugates being approved by the US Food and Drug Administration (FDA) for the treatment of hematologic and solid tumors [134].…”

Section: Anti-egfr Antibodiesmentioning

confidence: 99%

EGFR-Targeted Photodynamic Therapy

et al. 2022

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The epidermal growth factor receptor (EGFR) plays a pivotal role in the proliferation and metastatization of cancer cells. Aberrancies in the expression and activation of EGFR are hallmarks of many human malignancies. As such, EGFR-targeted therapies hold significant potential for the cure of cancers. In recent years, photodynamic therapy (PDT) has gained increased interest as a non-invasive cancer treatment. In PDT, a photosensitizer is excited by light to produce reactive oxygen species, resulting in local cytotoxicity. One of the critical aspects of PDT is to selectively transport enough photosensitizers to the tumors environment. Accordingly, an increasing number of strategies have been devised to foster EGFR-targeted PDT. Herein, we review the recent nanobiotechnological advancements that combine the promise of PDT with EGFR-targeted molecular cancer therapy. We recapitulate the chemistry of the sensitizers and their modes of action in PDT, and summarize the advantages and pitfalls of different targeting moieties, highlighting future perspectives for EGFR-targeted photodynamic treatment of cancer.

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Section: Anti-egfr Antibodiesmentioning

confidence: 99%

EGFR-Targeted Photodynamic Therapy

et al. 2022

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“…3,4 Promising preclinical data led to the clinical evaluation of dolastatin 10, 5 although it failed in human clinical trials exhibiting severe off-target cytotoxicity. 6 Nevertheless, it served as the parent compound for a number of structurally related clinical candidates conjugated to antibodies (antibody drug conjugates (ADCs)): monomethyl auristatin E (MMAE), 7,8 monomethyl auristatin F (MMAF), 9 auristatin PE (soblidotin), 10 and N-terminus 2-aminoisobutyric acid (Aib) acestatin D. 11 Still, dolastatin 10 is considered one of the most cytotoxic peptides among the dolastatin family. 12 Dolastatins contain unusual amino acids, dolaisoleucine (Dil) and dolaproine (Dap), assembled to valine and dimethyl valine amino acids (Figure 1).…”

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confidence: 99%

“…The viability assay was carried out with three human breast cancer cell lines: MDA MB 231 (triple-negative), BT474 (HER2-positive), and SKBR3 (HER2-positive). 8,26 The metabolic activities of the cells were measured after incubation for 96 h. The treatment of all three cell lines with dolastatinol showed a significantly reduced viability compared with that with MMAF, with the IC 50 ranging between 0.95 and 2.3 nM for dolastatinol (Figure 7A−C). Importantly, dolastatinol exhibited single-digit nanomolar potency on the triple-negative MDA MB 231 cell line (IC 50 = 1.54 nM), whereas MMAF was not active (Figure 7A).…”

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confidence: 99%

“…Dolastatin 10 exhibits cytotoxicity (subnanomolar range) that is more than two orders of magnitude higher than that of other tubulin-binding drugs from the Taxol and Vinka alkaloid families and remains in the cell longer due to much slower efflux. , Promising preclinical data led to the clinical evaluation of dolastatin 10, although it failed in human clinical trials exhibiting severe off-target cytotoxicity . Nevertheless, it served as the parent compound for a number of structurally related clinical candidates conjugated to antibodies (antibody drug conjugates (ADCs)): monomethyl auristatin E (MMAE), , monomethyl auristatin F (MMAF), auristatin PE (soblidotin), and N-terminus 2-aminoisobutyric acid (Aib) acestatin D . Still, dolastatin 10 is considered one of the most cytotoxic peptides among the dolastatin family …”

mentioning

confidence: 99%

“…Cells were treated with increasing concentrations of dolastatinol or MMAF, and their viability was monitored using the XTT assay to determine the half-maximal inhibitory concentration (IC 50 ). The viability assay was carried out with three human breast cancer cell lines: MDA MB 231 (triple-negative), BT474 (HER2-positive), and SKBR3 (HER2-positive). , …”

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confidence: 99%

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Discovery of Dolastatinol: A Synthetic Analog of Dolastatin 10 and Low Nanomolar Inhibitor of Tubulin Polymerization

Gutman

Bazylevich

Prasad

et al. 2021

ACS Med. Chem. Lett.

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We developed a highly potent anticancer agent, dolastatinol, which is a methylene hydroxyl derivative of dolastatin 10. Dolastatinol is a synthetic analog of dolastatin 10, synthesized by a solid-phase peptide Fmoc chemistry protocol on 2-chlorotrityl chloride resin utilizing a pH-triggering self-immolative monosuccinate linker. The introduction of the C-terminus hydroxyl methylene functionality preserves the anticancer properties of the parent dolastatin 10, including strong suppression of the cell proliferation, migration, high cytotoxicity. Our research establishes a new facile route toward the further development of C-terminus-modified dolastatin-10-based microtubule inhibitors for anticancer treatment.

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