Sacituzumab govitecan: an antibody–drug conjugate

Abstract

Despite advances in the diagnosis and treatment of patients with cancer, patients with metastatic cancer have limited therapeutic options after initial lines of therapy. Understanding tumor biology has translated into the identification of actionable targets that resulted in therapeutics. Antibody-drug conjugates (ADC) are capitalizing on this explosion of scientific information. ADCs allow an antibody to a unique target to be conjugated via an innovative linker, to a highly toxic drug which is delivered to its target. Sacituzumab govitecan is an ADC that combines the active molecule in irinotecan, SN-38, to an antibody targeting trop2. Areas covered: In this review, the authors introduce the reader to the ADC sacituzumab govitecan providing the reader with details about its pharmacokinetics, pharmacodynamics, efficacy and safety. The authors also give their expert analysis about its potential future use. Expert opinion: Sacituzumab govitecan is a novel and well-tolerated therapeutic showing promising results in difficult to treat cancers. Further studies are underway to optimize the group of patients that would benefit from it. Given its excellent performance, we are cautiously optimistic it will be approved by the FDA.

Sacituzumab Govitecan and Treatment Area

“…For this reason, an antigen found in tumor cells was wanted to be selected and in this way it was aimed to reduce toxicity. [1][2][3] These conjugates are drugs that select cancer cells in a specific way and have toxic effects on these cells. Due to its selectivity, it has high effect and less toxic effect on healthy body cells.…”

“…[4] It consists of the combination of SN-38, the active molecule of irinotecan, and an antibody targeting the TROP2 receptor. [3] Irinotecan is a topoisomerase inhibitor effective in lung, gastrointestinal and gynecological cancers. [1,9] During mitosis, cells stop dividing by affecting the S phase.…”

Immunotoxins: Targeted Toxin Delivery for Cancer Therapy

“…ADCs are molecules containing an mAb conjugated with a cytotoxic drug via a linker. 4,19,20 Early ADCs were composed of whole murine antibodies conjugated to a traditional chemotherapeutic drug. These attempts were not successful due to the rapid clearance caused by the nonspecific toxicity to normal cells and tissues, immunogenicity, insufficient anticancer potency of the conjugated cytotoxic agents, and limited internalization, thus the amount of the effector accumulated in the targeted cells was not enough to trigger cell death.…”

“…These attempts were not successful due to the rapid clearance caused by the nonspecific toxicity to normal cells and tissues, immunogenicity, insufficient anticancer potency of the conjugated cytotoxic agents, and limited internalization, thus the amount of the effector accumulated in the targeted cells was not enough to trigger cell death. 4,19,20 With experiences gained from these early explorations, several improvements were introduced in developing new ADCs. To date, there are three ADCs approved.…”

SN38-loaded <100 nm targeted liposomes for improving poor solubility and minimizing burst release and toxicity: in vitro and in vivo study

“…From unmet clinical need, rapid drug research and development is one of the strategies. 22,23 Liposomal formulations are a well-established technique in drug-delivery systems, and some were approved two decades ago. Since SN38 is unstable at physiological pH, the use of a liposomal structure can protect the drug against hydrolysis and achieve high stability.…”