Antibody-drug conjugates: Current status and future perspectives

Gébleux, Rémy; Casi, Giulio

doi:10.1016/j.pharmthera.2016.07.012

Cited by 51 publications

(62 citation statements)

References 148 publications

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“…Recently, greater efforts have been made to CD123 monoclonal antibody-based therapies against AML, e.g., the antibody-drug conjugates (ADCs). ADCs consist of highly specific antibodies and potent small molecule drugs, which are covalently conjugated via lysine or cysteine residues (Gebleux & Casi, 2016). Anti-CD123 antibody drug conjugates (CD123-CPT) were developed by integrating anti-CD123 antibody with camptothecin (CPT) via a disulfide linker (Li et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

“…Anti-CD123 antibody drug conjugates (CD123-CPT) were developed by integrating anti-CD123 antibody with camptothecin (CPT) via a disulfide linker (Li et al, 2016). Despite the demonstrated efficacy, such application suffered from a series of limitations (Gebleux & Casi, 2016). The instability of the linker has negative impact on ADC efficacy and therapeutic window, which often leads to serious 'offtarget' toxicities and even failure in clinical trials (Tsuchikama & An, 2016).…”

Section: Introductionmentioning

confidence: 99%

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Anti-CD123 antibody-modified niosomes for targeted delivery of daunorubicin against acute myeloid leukemia

et al. 2017

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A novel niosomal delivery system was designed and investigated for the targeted delivery of daunorubicin (DNR) against acute myeloid leukemia (AML). Anti-CD123 antibodies conjugated to Mal-PEG 2000 -DSPE were incorporated into normal niosomes (NS) via a post insertion method to afford antibody-modified niosomes (CD123-NS). Next, NS was modified with varying densities of antibody (0.5 or 2%, antibody/Span 80, molar ratio), thus providing L-CD123-NS and H-CD123-NS. We studied the effect of antibody density on the uptake efficiency of niosomes in NB4 and THP-1 cells, on which CD123 express differently. Our results demonstrate CD123-NS showed significantly higher uptake efficiency than NS in AML cells, and the uptake efficiency of CD123-NS has been ligand densitydependent. Also, AML cells preincubated with anti-CD123 antibody showed significantly reduced cellular uptake of CD123-NS compared to control. Further study on the uptake mechanism confirmed a receptor-mediated endocytic process. Daunorubicin (DNR)-loaded H-CD123-NS demonstrated a 2.45-and 3.22-fold higher cytotoxicity, compared to DNR-loaded NS in NB4 and THP-1 cells, respectively. Prolonged survival time were observed in leukemic mice treated with DNR-H-CD123-NS. Collectively, these findings support that the CD123-NS represent a promising delivery system for the treatment of AML. ARTICLE HISTORY

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Anti-CD123 antibody-modified niosomes for targeted delivery of daunorubicin against acute myeloid leukemia

et al. 2017

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“…A typical product is the antibody–drug conjugate (ADC), which is a broad class of molecules comprising of a potent cytotoxic agent conjugated with a mAb using a chemically stable linker . ADCs allow for the targeted delivery of cytotoxic agents to tumors while largely sparing normal cells lacking expression of the target antigen, which are being developed for the treatment of a variety of tumors . ADCs have demonstrated excellent tumor suppressing abilities in preclinical studies.…”

Section: Introductionmentioning

confidence: 99%

“…ADCs have demonstrated excellent tumor suppressing abilities in preclinical studies. However, a similar success is rarely observed in clinical trials . To date, three ADCs have been approved by the Food and Drug Administration (FDA): Gemtuzumab Ozogamicin (Mylotarg ® ; Pfizer, NY, USA), Brentuximab Vedotin (Adcetris ® ; Seattle Genetics, WA, USA), and Trastuzumab emtansine (T‐DM1, Kadcyla ® , Roche, Basel, Switzerland) .…”

Section: Introductionmentioning

confidence: 99%

“…However, a similar success is rarely observed in clinical trials . To date, three ADCs have been approved by the Food and Drug Administration (FDA): Gemtuzumab Ozogamicin (Mylotarg ® ; Pfizer, NY, USA), Brentuximab Vedotin (Adcetris ® ; Seattle Genetics, WA, USA), and Trastuzumab emtansine (T‐DM1, Kadcyla ® , Roche, Basel, Switzerland) . However, Mylotarg was voluntarily withdrawn from the market in 2010 because of failing to demonstrate its clinical benefit in two Phase III studies .…”

Section: Introductionmentioning

confidence: 99%

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Novel reduction‐sensitive micellar nanoparticles assembled from Rituximab–doxorubicin conjugates as smart and intuitive drug delivery systems for the treatment of non‐Hodgkin's lymphoma

et al. 2017

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In this study, a novel reduction-sensitive drug delivery system, the rituximab-doxorubicin (RTX-DOX) micellar nanoparticle (RDMN), was specially designed for targeted delivery and release of DOX in non-Hodgkin's lymphoma (NHL) cells. The RDMN was fabricated by self-assembling of amphiphilic RTX-DOX conjugates (RDCs), which were synthesized by conjugating the hydrophilic Fab fragments of RTX (an anti-CD20 monoclonal antibody) and hydrophobic DOXs by a reduction-responsive linker, 3-(2-Pyridyldithio) propionyl hydrazide (PDPH). The RDMNs were characterized via dynamic light scattering and transmission electron microscopy, both showed the sizes of approximately 94.1 ± 14.5 nm with a uniform size distribution. Polyplex dissociation, which was indicated by accelerated DOX release rate and increased particle size, was observed in the presence of 2.5 mm 1,4-dithiothreitol due to the cleavage of disulfide bonds in PDPH linkers. In vitro transfection assays against human NHL cell line, JeKo-1, showed significantly increased uptake for RDMNs, as compared to RDCs and free RTX/DOX. Both in and ex vivo experiments demonstrated that RDMNs showed the highest therapeutic effect among all the experimental groups. These results suggested that this RDMN could be a potential, safe and efficient drug delivery vector, which deserves further investigation in the clinic.

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

Guo

et al. 2021

Cancer Medicine

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Antibody-drug conjugates: Current status and future perspectives

Cited by 51 publications

References 148 publications

Anti-CD123 antibody-modified niosomes for targeted delivery of daunorubicin against acute myeloid leukemia

Anti-CD123 antibody-modified niosomes for targeted delivery of daunorubicin against acute myeloid leukemia

Novel reduction‐sensitive micellar nanoparticles assembled from Rituximab–doxorubicin conjugates as smart and intuitive drug delivery systems for the treatment of non‐Hodgkin's lymphoma

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

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