Site-Specific Conjugation to Cys-Engineered THIOMAB™ Antibodies

Preclinical optimization of Ly6E-targeted ADCs for increased durability and efficacy of anti-tumor response

“…ADCs were made from antibodies containing the LC K149C mutation, termed ThioMabs, essentially as described. 55 All conjugates were generated with less than 5% aggregate and at DAR >1.8.…”

A homogeneous high-DAR antibody–drug conjugate platform combining THIOMAB antibodies and XTEN polypeptides

“…37 Anti-CD22, anti-Her2 and anti-WTA THIOMAB antibodies for conjugate generation are Cys mutants of those discovered previously and were deblocked prior to conjugation. 10,25,38,39 All other reagents were obtained from commercial vendors unless otherwise indicated. All animal studies were carried out in compliance with National Institutes of Health guidelines for the care and use of laboratory animals and were approved by the Institutional Animal Care and Use Committee at Genentech, Inc.…”

“…24 Similarly, cysteine-engineered THIOMAB antibodies enable site-specic, homogeneous conjugation of payloads to antibodies. 23,25 Thus, combining XTEN and THIOMABs in TXCs was expected to provide ne control over all aspects of conjugate composition and avoid payload insertion at interchain disulde linkages, capabilities lacking in previous high-DAR ADC approaches. We applied our TXC approach across three different payloadsa microtubule destabilizing agent, a DNA monoalkylator and an antibiotic.…”

Antibody–Drug Conjugates for the Treatment of Acute Pediatric Leukemia

“…DCLL9718S is a THIOMAB TM antibody-drug conjugated (TDC) consisting of an IgG1 anti-CLL1 antibody linked to two PBD dimers via a cleavable disulfide linker. THIOMAB TM consists of engineering a recombinant mutation of one or more amino acids to a cysteine which allows the ADC to achieve improved stability of the connection of cytotoxic drug to antibody [72]. A clinical trial examined 18 adult patients with relapsed or refractory AML in a phase I trial of DCLL9718S [73].…”