Antibody-drug conjugates (ADCs) have become promising therapy for the treatment of cancers. Among all the ADCs under development, 2/3 of them are interchain cysteine-linked ADCs. The ADCs are manufactured by partially reducing the 4 pairs of interchain disulfide bonds followed by conjugate cytotoxic payloads to the thiols, as a consequence, the antibodies are linked with 0, 2, 4, 6, 8 drugs. The drug-to-antibody ratio (DAR) and the drug linking position are important parameters that affect the therapeutic effects and need to be well characterized. In this study, we successfully characterize a method for the interchain cysteine linked ADC in a biological matrix.

In this infographic, we describe various mass spectrometry-based strategies Frontage has successfully applied in the bioanalysis of ADCs for clinical and preclinical studies. Antibody-drug conjugates (ADCs) combine the best of two modalities: toxin efficacy and antibody specificity. The result is an improved therapeutic window with fewer side effects but the bioanalytical requirements for PK analysis also require a multifaceted approach.

Oligonucleotide (OGN) therapy is increasingly recognized as an important therapeutic modality with the promise of curing diseases. However, unlike most biotherapeutics, the development of OGN drugs often requires their determination with high sensitivity and specificity in multiple, complex biologic matrices such as blood and tissues in order to measure their exposure and distribution for understating PK, PD, and safety.

At Frontage Laboratories (PA, USA), we have developed highly sensitive and specific quantitative methods for the determination of OGN in plasma and tissues using hybridization immunoassay and LC–MS techniques. In this webinar, we will present the method development, validation, and comparison of these techniques for the quantification of OGN as well as a case study with antisense OGN.