Dear Nagarjun,

The followings are recent publications on this field which may be helpful:

1-Review

Methods to Design and Synthesize Antibody-Drug

Conjugates (ADCs)

Houzong Yao 1,†, Feng Jiang 1,2,†, Aiping Lu 1,* and Ge Zhang

Abstract: Antibody-drug conjugates (ADCs) have become a promising targeted therapy strategy that combines the specificity, favorable pharmacokinetics and biodistributions of antibodies with the destructive potential of highly potent drugs. One of the biggest challenges in the development of ADCs is the application of suitable linkers for conjugating drugs to antibodies. Recently, the design and synthesis of linkers are making great progress. In this review, we present the methods that are currently used to synthesize antibody-drug conjugates by using thiols, amines, alcohols, aldehydes

and azides.

To view the full review article, please see attached file.

2-Research review paper

Current methods for the synthesis of homogeneous antibody–drug conjugates

Alicja M. Sochaj, Karolina W. Świderska, Jacek Otlewski

Abstract

Development of efficient and safe cancer therapy is one of the major challenges of the modern medicine. Over the last few years antibody–drug conjugates (ADCs) have become a powerful tool in cancer treatment with two of them, Adcetris® (brentuximab vedotin) and Kadcyla® (ado-trastuzumab emtansine), having recently been approved by the Food and Drug Administration (FDA). Essentially, an ADC is a bioconjugate that comprises a monoclonal antibody that specifically binds tumor surface antigen and a highly potent drug, which is attached to the antibody via either cleavable or stable linker. This approach ensures specificity and efficacy in fighting cancer cells, while healthy tissues remain largely unaffected.

Conventional ADCs, that employ cysteine or lysine residues as conjugation sites, are highly heterogeneous. This means that the species contain various populations of the ADCs with different drug-to-antibody ratios (DARs) and different drug load distributions. DAR and drug-load distribution are essential parameters of ADCs as they determine their stability and efficacy. Therefore, various drug-loaded forms of ADCs (usually from zero to eight conjugated molecules per antibody) may have distinct pharmacokinetics (PK) in vivo and may differ in clinical performance. Recently, a significant progress has been made in the field of site-specific conjugation which resulted in a number of strategies for synthesis of the homogeneous ADCs. This review describes newly-developed methods that ensure homogeneity of the ADCs including use of engineered reactive cysteine residues (THIOMAB), unnatural amino acids, aldehyde tags, enzymatic transglutaminase- and glycotransferase-based approaches and novel chemical methods. Furthermore, we briefly discuss the limitation of these methods emphasizing the need for further improvement in the ADC design and development.

http://www.sciencedirect.com/science/article/pii/S073497501530001X

3-Expert Review

Methods to Make Homogenous Antibody Drug Conjugates

Toni Kline & Alexander R. Steiner & Kalyani Penta & Aaron K. Sato & Trevor J. Hallam & Gang Yin

Pharm Res

DOI 10.1007/s11095-014-1596-8

ABSTRACT Antibody drug conjugates (ADCs) have progressed from hypothesis to approved therapeutics in less than 30 years, and the technologies available to modify both the antibodies and the cytotoxic drugs are expanding rapidly. For reasons well reviewed previously, the field is trending strongly toward homogeneous, defined antibody conjugation. In this review we present the antibody

and small molecule chemistries that are currently used and being explored to develop specific, homogenous ADCs.

4-Review Article

AAPS J. 2015 Mar; 17(2): 339–351.

Published online 2015 Jan 22. doi: 10.1208/s12248-014-9710-8

PMCID: PMC4365093

Antibody Drug Conjugates: Design and Selection of Linker, Payload and Conjugation Chemistry

Jessica R. McCombs and Shawn C. Owencorresponding author

Abstract

Antibody drug conjugates (ADCs) have emerged as an important pharmaceutical class of drugs designed to harness the specificity of antibodies with the potency of small molecule therapeutics. The three main components of ADCs are the antibody, the linker, and the payload; the majority of early work focused intensely on improving the functionality of these pieces. Recently, considerable attention has been focused on developing methods to control the site and number of linker/drug conjugated to the antibody, with the aim of producing more homogenous ADCs. In this article, we review popular conjugation methods and highlight recent approaches including “click” conjugation and enzymatic ligation. We discuss current linker technology, contrasting the characteristics of cleavable and non-cleavable linkers, and summarize the essential properties of ADC payload, centering on chemotherapeutics. In addition, we report on the progress in characterizing to determine physicochemical properties and on advances in purifying to obtain homogenous products. Establishing a set of selection and analytical criteria will facilitate the translation of novel ADCs and ensure the production of effective biosimilars.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4365093/

5-A Review on a Book

MAbs. 2014 Jan 1; 6(1): 30–33.

Published online 2013 Nov 1. doi: 10.4161/mabs.27005

PMCID: PMC3929452

Review of Antibody-Drug Conjugates, Methods in Molecular Biology series

A book edited by Laurent Ducry

Alain Beck*

Antibody-drug conjugates (ADCs) represent an exciting and promising therapeutic approach for the treatment of cancers. The US Food and Drug Administration’s recent approval of brentuximab vedotin (Adcetris®) in 2011 and trastuzumab emtansine (Kadcyla®) in 2013 has brought a proof of the ADC concept in hematologic and solid tumors, respectively. The number of ADCs or immunoconjugates undergoing clinical studies is rapidly increasing, driving much attention to understand the criteria for success. The ADC concept looks quite simple. The basic idea is to conjugate a potent cytotoxic drug to a monoclonal antibody (mAb) selected to target a tumor associated antigen. Both drug components are conjugated by a linker designed to be stable in the blood streamline and to properly release the drug into the targeted cancer cell. Tremendous progress has been made in each area (i.e., antibody, drug, linker, target), but many important parameters must be addressed simultaneously to make a successful ADC product. The aim of Antibody-Drug Conjugates, which was edited by Laurent Ducry (Lonza),1 is to provide detailed protocols for many of the critical ADC techniques necessary to succeed in the field. Each chapter addresses a specific aspect and is written by scientists who have recognized expertise in the domain.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3929452/

6-A Book

Ducry, Laurent (Ed.) Antibody Drug Conjugates. In: Methods in Molecular Biology. Book 1045. New York (NY); Humana Press; 2013.

Hoping this will be helpful,

Rafik

Dear Rafik, Thank you very much for the literature.

Hi Nagarjun. I strongly recommend the book "Bioconjugate Techniques" by Craig T. Hermanson.

It has in depth discussion and the chemistry of  Ab conjugation.

Thank Steingrimur Stefansson for your suggestion, I will look into the recommended book.