Antibody–Drug Conjugates for Immunology

Abstract

The application of antibody–drug conjugates (ADCs) to fields outside of oncology is increasing but is still relatively uncommon. A recent publication describes the conjugation of glucocorticoid receptor modulators to antibodies as a means of improving the separation between desired anti-inflammatory activity and unwanted systemic side effects.

Payload diversification: a key step in the development of antibody–drug conjugates

“…Two original ADCs (ABBV-3373 and ABBV-154) containing a glucocorticoid receptor modulator (GRM) are being clinically evaluated for the treatment of rheumatoid arthritis and Crohn’s disease (Table 2 , NCT03823391, NCT04888585, NCT05068284 and NCT04972968). Other immunology ADC payloads are being investigated in preclinical settings and could constitute an emerging class in ADC design [ 233 , 234 ]. In addition, an A-rifamycin derivative, that demonstrated promising results in preclinical evaluation [ 235 ], has been investigated in phase 1 clinical trials in patients with Staphylococcus aureus bacteremia (NCT03162250).…”

“…Non-internalizing ADCs would particularly benefit from newer payloads that present a strong bystander killing effect [227] or that are directed against extracellular or stromal targets [228], as exemplified by the PNU-159682-based ADC targeting tenascin-C, the inhibition of matrix metalloproteinase extracellular protein or more recently the inhibition of carbonic anhydrases [116,229,230] (Table 3). Interestingly ADC technology is also being explored in nononcological indications [231,232]. Two original ADCs (ABBV-3373 and ABBV-154) containing a glucocorticoid receptor modulator (GRM) are being clinically evaluated for the treatment of rheumatoid arthritis and Crohn's disease (Table 2, NCT03823391, NCT04888585, NCT05068284 and NCT04972968).…”

Antibody–drug conjugates: Recent advances in payloads

“…17 B and C). Peter S. Dragovich 127 synthetically tested a variety of analogs containing different amine substituent acetal groups. Among them, piperazine compound 99 exhibits cellular activity like dexamethasone ( 97 ) and compound 98 (GRE cell, + mTNF, IC 50 = 33 nmol/L).…”

Recent Advances in Bioconjugated Transition Metal Complexes for Cancer Therapy

“…Specific sequences of amino acids form complex structures known as peptides and proteins, which are biomolecules involved in a wide range of organism vital functions. In recent times, amino acid derivatives have been investigated as anticancer agents, and in particular, poli-peptides [73] and antibodies [74,75] have been largely included in studies based on the immunotherapeutic approach. Furthermore, they can be conjugated with a metal-based scaffold in order to deliver the active moiety to the desired target taking advantage of their biocompatibility.…”