Advancements in Linking Technology Re-instilling the Hope in ADC Industry

NOIDA, India - March 24, 2017 - PRLog -- Site specific antibodies conjugated to cytotoxic drugs - the answer to cancer when they were first developed. This technology dates back to 90's, and early work is focused on the use of clinically approved drugs, but no attention was paid to the particular aspects of the mAb carrier, the mode of drug attachment and mechanism of drug release. Therefore, past attempts to develop ADCs were hindered by the inability to produce stable combinations.

Significant advancements in the past few years have again fuelled interest in ADCs. These advancements include improvements in linking technologies, which has helped in the development of drugs, such as ADCETRIS and Kadcyla. Still, only a very small amount of cytotoxic agent makes it to the cell, about 1.5% of the total dose.

According to a new research report by RNCOS entitled, "Global Antibody Drug Conjugates Market By Drug (ADCETRIS, Kadcyla), Pipeline Analysis (By Phase, Mode of Action, Linker, Technology, and Indication) Outlook 2022", in order to overcome these issues, the industry is coming up with more precise and optimal positioning of the link between the cytotoxin and the antibody, resulting in a "homogeneous" product that may assure more efficient delivery of cytotoxin to the tumor cell, resulting in better efficacy and less toxicity. Preclinical studies with precise linking technologies, such as Genentech's ThioMab technology, have already shown that the therapeutic index, the ratio between efficacy and tolerability, can be improved. Moreover, scientists at the Scripps Research Institute have developed improved linkages in the form of Thiol-Click reaction. They have described a way to make improved linkages using compounds based on methylsulfonyl-substituted heterocycles instead of maleimides. The method turns out to enable more stable and specific linkages.

Research also showed that, PolyTherics has come up with ThioBridge conjugation and linker technology. The process avoids random conjugation of ADC payload, which would result in multiple positional isomers with potentially different bioactivity, pharmacokinetics, distribution, immunogenicity, safety, and stability profiles. In different tests using trastuzumab as the exemplar antibody, ThioBridge conjugates were found to be stable in human serum, while maleimide conjugates were observed to be unstable and underwent payload de-conjugation and cross-conjugation to serum proteins, with evidence of antibody fragmentation. Owing to such advancements in linking technology used in developing ADCs, the ADCs industry is expected to flourish at a faster pace in the coming years.

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