scholarly journals Antibody–drug conjugates and other nanomedicines: the frontier of gynaecological cancer treatment

2016 ◽  
Vol 6 (6) ◽  
pp. 20160054 ◽  
Author(s):  
David Howard ◽  
Jetzabel Garcia-Parra ◽  
Gareth D. Healey ◽  
Cynthia Amakiri ◽  
Lavinia Margarit ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Clinical Trials ◽  
Cancer Therapy ◽  
Rational Design ◽  
State Of The Art ◽  
Cervix Uterus ◽  
Antibody Drug Conjugates ◽  
Drug Conjugates ◽  
Liposomal Drugs ◽  
Antibody Drug

Gynaecological cancers: malignancies of the cervix, uterus, ovaries, vagina and vulva, are responsible for over 1.1 million new cancer cases and almost half a million deaths annually. Ovarian cancer in particular is difficult to treat due to often being diagnosed at a late stage, and the incidence of uterine and vulvar malignancies are both on the rise. The field of nanomedicine is beginning to introduce drugs into the clinic for oncological applications exemplified by the liposomal drugs, Doxil and Myocet, the nanoparticle, Abraxane and antibody–drug conjugates (ADCs), Kadcyla and Adcetris. With many more agents currently undergoing clinical trials, the field of nanomedicine promises to have a significant impact on cancer therapy. This review considers the state of the art for nanomedicines currently on the market and those being clinically evaluated for the treatment of gynaecological cancers. In particular, it focuses on ADCs and presents a methodology for their rational design and evaluation.

HER2-targeted antibody drug conjugates for ovarian cancer therapy

2016 ◽  
Vol 93 ◽  
pp. 274-286 ◽  
Author(s):  
Jing Jiang ◽  
Lihou Dong ◽  
Lei Wang ◽  
Ling Wang ◽  
Jing Zhang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Therapy ◽  
Antibody Drug Conjugates ◽  
Drug Conjugates ◽  
Antibody Drug

scholarly journals Targeting RON receptor tyrosine kinase for treatment of advanced solid cancers: antibody–drug conjugates as lead drug candidates for clinical trials

2020 ◽  
Vol 12 ◽  
pp. 175883592092006
Author(s):  
Hang-Ping Yao ◽  
Sreedhar Reddy Suthe ◽  
Xiang-Min Tong ◽  
Ming-Hai Wang
Keyword(s):  
Clinical Trials ◽  
Tyrosine Kinase ◽  
Receptor Tyrosine Kinase ◽  
Targeted Therapeutics ◽  
Antibody Drug Conjugates ◽  
Drug Candidates ◽  
Drug Conjugates ◽  
Ron Receptor ◽  
Antibody Drug

The recepteur d’origine nantais (RON) receptor tyrosine kinase, belonging to the mesenchymal-to-epithelial transition proto-oncogene family, has been implicated in the pathogenesis of cancers derived from the colon, lung, breast, and pancreas. These findings lay the foundation for targeting RON for cancer treatment. However, development of RON-targeted therapeutics has not gained sufficient attention for the last decade. Although therapeutic monoclonal antibodies (TMABs) targeting RON have been validated in preclinical studies, results from clinical trials have met with limited success. This outcome diminishes pharmaceutical enthusiasm for further development of RON-targeted therapeutics. Recently, antibody–drug conjugates (ADCs) targeting RON have drawn special attention owing to their increased therapeutic activity. The rationale for developing anti-RON ADCs is based on the observation that cancer cells are not sufficiently addicted to RON signaling for survival. Thus, TMAB-mediated inhibition of RON signaling is ineffective for clinical application. In contrast, anti-RON ADCs combine a target-specific antibody with potent cytotoxins for cancer cell killing. This approach not only overcomes the shortcomings in TMAB-targeted therapies but also holds the promise for advancing anti-RON ADCs into clinical trials. In this review, we discuss the latest advancements in the development of anti-RON ADCs for targeted cancer therapy including drug conjugation profile, pharmacokinetic properties, cytotoxic effect in vitro, efficacy in tumor models, and toxicological activities in primates.

scholarly journals Antibody–Drug Conjugates for Cancer Therapy

Molecules ◽  
2020 ◽  
Vol 25 (20) ◽  
pp. 4764
Author(s):  
Umbreen Hafeez ◽  
Sagun Parakh ◽  
Hui K. Gan ◽  
Andrew M. Scott
Keyword(s):  
Monoclonal Antibody ◽  
Molecular Imaging ◽  
Cancer Therapy ◽  
Normal Tissue ◽  
Clinical Development ◽  
Antibody Drug Conjugates ◽  
Drug Conjugates ◽  
Novel Drugs ◽  
Antibody Drug

Antibody–drug conjugates (ADCs) are novel drugs that exploit the specificity of a monoclonal antibody (mAb) to reach target antigens expressed on cancer cells for the delivery of a potent cytotoxic payload. ADCs provide a unique opportunity to deliver drugs to tumor cells while minimizing toxicity to normal tissue, achieving wider therapeutic windows and enhanced pharmacokinetic/pharmacodynamic properties. To date, nine ADCs have been approved by the FDA and more than 80 ADCs are under clinical development worldwide. In this paper, we provide an overview of the biology and chemistry of each component of ADC design. We briefly discuss the clinical experience with approved ADCs and the various pathways involved in ADC resistance. We conclude with perspectives about the future development of the next generations of ADCs, including the role of molecular imaging in drug development.

scholarly journals Therapeutic Monoclonal Antibodies and Antibody Products: Current Practices and Development in Multiple Myeloma

Cancers ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 15 ◽  
Author(s):  
Francesca Bonello ◽  
Roberto Mina ◽  
Mario Boccadoro ◽  
Francesca Gay
Keyword(s):  
Multiple Myeloma ◽  
Clinical Trials ◽  
Monoclonal Antibodies ◽  
T Cell ◽  
Plasma Cells ◽  
Antibody Drug Conjugates ◽  
Drug Conjugates ◽  
Promising Target ◽  
Therapeutic Monoclonal Antibodies ◽  
Antibody Drug

Immunotherapy is the latest innovation for the treatment of multiple myeloma (MM). Monoclonal antibodies (mAbs) entered the clinical practice and are under evaluation in clinical trials. MAbs can target highly selective and specific antigens on the cell surface of MM cells causing cell death (CD38 and CS1), convey specific cytotoxic drugs (antibody-drug conjugates), remove the breaks of the immune system (programmed death 1 (PD-1) and PD-ligand 1/2 (L1/L2) axis), or boost it against myeloma cells (bi-specific mAbs and T cell engagers). Two mAbs have been approved for the treatment of MM: the anti-CD38 daratumumab for newly-diagnosed and relapsed/refractory patients and the anti-CS1 elotuzumab in the relapse setting. These compounds are under investigation in clinical trials to explore their synergy with other anti-MM regimens, both in the front-line and relapse settings. Other antibodies targeting various antigens are under evaluation. B cell maturation antigens (BCMAs), selectively expressed on plasma cells, emerged as a promising target and several compounds targeting it have been developed. Encouraging results have been reported with antibody drug conjugates (e.g., GSK2857916) and bispecific T cell engagers (BiTEs®), including AMG420, which re-directs T cell-mediated cytotoxicity against MM cells. Here, we present an overview on mAbs currently approved for the treatment of MM and promising compounds under investigation.

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