scholarly journals Antibody-Drug Conjugates: A Promising Novel Therapy for the Treatment of Ovarian Cancer

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2223
Author(s):  
Aranzazu Manzano ◽  
Alberto Ocaña
Keyword(s):  
Ovarian Cancer ◽  
Therapeutic Strategy ◽  
Membrane Surface ◽  
Chemotherapeutic Agents ◽  
Novel Therapy ◽  
Antibody Drug Conjugates ◽  
Drug Conjugates ◽  
Specific Antigens ◽  
Early Phase Clinical Trials ◽  
Antibody Drug

Antibody-drug conjugates (ADCs) represent a novel and promising therapeutic strategy for the treatment of cancer patients. ADCs target antigens highly expressed on the membrane surface of tumor cells to selectively deliver a cytotoxic drug. Ovarian tumors differentially express tumor-specific antigens, which can be used to guide ADCs. This strategy allows for optimizing tumor targeting while minimizing systemic toxicity compared to classical chemotherapeutic agents. ADCs can be improved by using a cleavable linker allowing the delivery of the toxic payload in surrounding cells not expressing the target protein, therefore acting on heterogeneous tumors with different cell populations. Currently, more than 15 ADCs are under preclinical investigation in ovarian cancer, and some of them have already been tested in early-phase clinical trials with promising results. In this review, we summarize the mechanism of action and the toxicity profile of ADCs and discuss the latest preclinical discoveries and forthcoming applications in ovarian cancer.

Antibody-Drug Conjugates in Hematologic Malignancies

2013 ◽  
pp. e108-e113
Author(s):  
Lori A. Leslie ◽  
Anas Younes
Keyword(s):  
Hematologic Malignancies ◽  
Cytotoxic Agents ◽  
Clinical Value ◽  
Suppressor Activity ◽  
Antibody Drug Conjugates ◽  
Drug Conjugates ◽  
Tumor Suppressor Activity ◽  
Cytotoxic Molecules ◽  
Early Phase Clinical Trials ◽  
Antibody Drug

Antibody-drug conjugates (ADCs) are agents composed of a monoclonal antibody linked to cytotoxic molecules. By specifically delivering cytotoxic agents to cells expressing surface antigens of interest, ADC technology allows for the targeted use of highly toxic agents resulting in increased efficacy against malignant cells and decreased damage to normal tissue. Effector agents can be small molecules, radioisotopes, proteins, or bacterially derived toxins. Over the past several decades, ADCs have been evaluated in a variety of preclinical models of hematologic malignancies, as well as early-phase clinical trials with limited success. More recently, advancements in linkage technology, improvements in cytotoxin selection, and use of smaller conjugates containing partial rather than complete antibodies have drastically improved the potential clinical value of ADCs. In the future, ADC technology may be used to restore tumor suppressor activity, target the microenvironment, or replace nonfunctional enzymes. In this review we will discuss select ADCs in various stages of development for use in hematologic malignancies including lymphoma, multiple myeloma, and leukemia.

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.

Antibody Drug Conjugates in the Treatment of Epithelial Ovarian Cancer

2018 ◽  
Vol 32 (6) ◽  
pp. 1057-1071 ◽  
Author(s):  
Debra L. Richardson ◽  
Shelly M. Seward ◽  
Kathleen N. Moore
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Antibody Drug Conjugates ◽  
Drug Conjugates ◽  
Antibody Drug

scholarly journals Human Antibody Fusion Proteins/Antibody Drug Conjugates in Breast and Ovarian Cancer

2017 ◽  
Vol 44 (5) ◽  
pp. 303-310 ◽  
Author(s):  
Eden R. Padayachee ◽  
Fleury Augustin Nsole Biteghe ◽  
Zaria Malindi ◽  
Dirk Bauerschlag ◽  
Stefan Barth
Keyword(s):  
Ovarian Cancer ◽  
Fusion Proteins ◽  
Human Antibody ◽  
Breast And Ovarian Cancer ◽  
Antibody Drug Conjugates ◽  
Drug Conjugates ◽  
Antibody Drug

Novel mesothelin antibody-drug conjugates: current evidence and future role in the treatment of ovarian cancer

2021 ◽  
pp. 1-10
Author(s):  
Dennis Mauricio ◽  
Justin Harold ◽  
Joan R. Tymon-Rosario ◽  
Burak Zeybek ◽  
Alessandro D. Santin
Keyword(s):  
Ovarian Cancer ◽  
Current Evidence ◽  
Future Role ◽  
Antibody Drug Conjugates ◽  
Drug Conjugates ◽  
Antibody Drug

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 Antibody-drug conjugates with dual payloads for combating breast tumor heterogeneity and drug resistance

2020 ◽  
Author(s):  
Chisato M. Yamazaki ◽  
Aiko Yamaguchi ◽  
Yasuaki Anami ◽  
Wei Xiong ◽  
Yoshihiro Otani ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Breast Tumor ◽  
Tumor Heterogeneity ◽  
Chemotherapeutic Agents ◽  
Specific Cell ◽  
Antibody Drug Conjugates ◽  
Drug Conjugates ◽  
Dual Drug ◽  
Antibody Drug

ABSTRACTBreast tumors generally consist of a diverse population of cells with varying gene expression profiles. Breast tumor heterogeneity is a major factor contributing to drug resistance, recurrence, and metastasis after chemotherapy. Antibody-drug conjugates (ADCs) are emerging chemotherapeutic agents with striking clinical success, including T-DM1 for HER2-positive breast cancer. However, these ADCs often suffer from issues associated with intratumor heterogeneity. Here, we show that homogeneous ADCs containing two distinct payloads are a promising drug class for addressing this clinical challenge. Our conjugates show HER2-specific cell killing potency, desirable pharmacokinetic profiles, minimal immunogenicity, and marginal toxicity at therapeutic doses. Notably, a dual-drug ADC exerts greater treatment effect and survival benefit than does co-administration of two single-drug variants in a xenograft mouse model representing intratumor HER2 heterogeneity and elevated drug resistance. Our findings highlight the therapeutic potential of the dual-drug ADC format for treating refractory breast cancer and perhaps other cancers.

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