Antibody‐drug therapeutic conjugates: Potential of antibody‐siRNAs in cancer therapy

Abstract

Codelivery is a promising strategy of targeted delivery of cytotoxic drugs for eradicating tumor cells. This rapidly growing method of drug delivery uses a conjugate containing drug linked to a smart carrier. Both two parts usually have therapeutic properties on the tumor cells. Monoclonal antibodies and their derivatives, such as Fab, scFv, and bsAb due to targeting high potent have now been attractive candidates as drug targeting carrier systems. The success of some therapeutic agents like small interfering RNA (siRNA), a small noncoding RNAs, with having problems such as enzymatic degradation and rapid renal filtration need to an appropriate carrier. Therefore, the aim of this study is to review the recent enhancements in development of antibody drug conjugates (ADCs), especially antibody–siRNA conjugates (SRCs), its characterizations and mechanisms in innovative cancer therapy approaches.

Antibody Conjugates-Recent Advances and Future Innovations

“…Examples of linker payloads as well as formulation and delivery challenges for non-oncology indications are discussed below. Additionally, genes of interest have been targeted in specific cell types to produce durable response using antibody-oligonucleotide conjugates [54,55]. Delivery of oligonucleotides have traditionally been challenging and various modifications have been employed to facilitate better cell penetration.…”

Importance and Considerations of Antibody Engineering in Antibody-Drug Conjugates Development from a Clinical Pharmacologist’s Perspective

“…A final novel antibody approach is in the use of nanobodies (i.e., small immunoproteins [SIPs] and single-chain variable fragments [scFv]) [211,212]. These antibodies are currently primarily derived from camelids (e.g., camels, llamas, alpacas) which utilize a unique heavy-chain only antibody conformation [211,213].…”

Oncogenic and tumor suppressor function of MEIS and associated factors

“…Noncoding RNAs, especially siRNAs and lncRNAs, have the potential to be used as chemotherapeutic agents in cancer treatments (Drosopoulos and Linardopoulos, 2019). siRNA, which is a double-stranded RNA molecule with a length of 20-25 base pairs, is complementary to the mRNA of the specific gene (Yarian et al, 2019). Therefore, the expression level of an oncogene can be targeted by limiting the translation level with siRNA treatments (Drosopoulos and Linardopoulos, 2019;Yarian et al, 2019).…”

“…siRNA, which is a double-stranded RNA molecule with a length of 20-25 base pairs, is complementary to the mRNA of the specific gene (Yarian et al, 2019). Therefore, the expression level of an oncogene can be targeted by limiting the translation level with siRNA treatments (Drosopoulos and Linardopoulos, 2019;Yarian et al, 2019). Several siRNAs have been shown to reduce cancer proliferation, metastasis, invasion, and impaired cell cycle (Yarian et al, 2019).…”

“…Therefore, the expression level of an oncogene can be targeted by limiting the translation level with siRNA treatments (Drosopoulos and Linardopoulos, 2019;Yarian et al, 2019). Several siRNAs have been shown to reduce cancer proliferation, metastasis, invasion, and impaired cell cycle (Yarian et al, 2019). In addition, some siRNAs could stimulate apoptosis in PC, OSCC, lung cancer, nasopharyngeal carcinoma, osteosarcoma, and others (Feng et al, 2017;Liu et al, 2017;Shi et al, 2018;Wang et al, 2018c;Wang et al, 2018d;Wang et al, 2018e; miRNAs could act as tumor suppressors or oncogenes (Calin et al, 2002;Peng and Croce, 2016).…”