Techniques for Producing Antibodies to Drug Conjugates

Chemists have been experimenting with the potential of drug conjugates since 1975, when Nobel prize-winners Georges Köhler and César Milstein successfully produced the first monoclonal antibodies. They achieved this by drawing B lymphocytes from a biological host that was infected with a specific antigen, and fusing them with myeloma to produce a self-replicating cell line known as a hybridoma. These hybrid cell lines are cultured in laboratory environments from a single viable hybridoma cell, resulting in multiple genetically reproduced, or cloned, cells.

Hybridoma are capable of consistent replication, and antibody production, enabling researchers to culture antigen-specific antibodies in vitro with exceptional degrees of reproducibility. This was the first step towards synthesizing drug conjugates for immunoassay equipment and emerging pharmaceuticals.

Researchers hoped to take advantage of the excellent target-specificity of monoclonal antibodies by covalently binding them with drugs or proteins, producing antigen-specific reactions that would bind to antigenic cells, either detecting or attacking them. This required stable chemical linkers such as thiols, amines, alcohols, or aldehydes, to suitably attach drug molecules to monoclonal antibodies.

Both heterogenous and homogenous methods are used for producing drug conjugates, but perhaps the most common drug conjugates are synthesized through homogenous binding of drug molecules to cysteine residues in monoclonal antibodies. The interchain disulfide bonds of the monoclonal antibody are reduced, generating free thiol groups that act as attachment sites on the antibody surface. Other methods for synthesizing drug conjugates include:

• Amide formation;
• Ether bond formation;
• Expressed protein ligation (EPL);
• FGE conjugation.

Synthesizing potent drug conjugates requires a thorough understanding of this relationship between antibody, linker, and drug. Advances in each preparatory area have given researchers the capacity for creating drug conjugates with non-cleavable and cleavable linkers, which display high variances in capacity and capability.

Established applications for high-potency drug conjugations include toxicology screening regents for EIA or ELISA testing equipment, while developers continue to study the potential of drug conjugates with cytotoxic payloads for highly targeted cancer treatments methods.

Drug Conjugates from Pyxis Laboratories

Pyxis Laboratories was established in 1997 on a foundation of research, development, and production expertise in the fields of specialty regents for diagnostic and pharmaceutical applications. The company is known for producing exceptional drug conjugates for multi-disciplinary applications, providing an established range of products such as:

• Alcohol such as, ethyl glucuronide-BSA (EtG-BSA);
• Amphetamines such as, Amphetamine-BSA, Methamphetamine-BSA, methcathinone-BSA, MDMA-BSA, MDPV-BSA, Mephedrone-BSA and Methylphenidate-BSA (Ritalin-BSA);
• Benzodiazepines, such as Oxazepam-BSA and Clonazepam-BSA;
• Cannabinoids such us, delta-8-THC-BSA, delta-9-THC-BSA; and synthetic cannabinoids such as, JWH-018-BSA, ABpinaca-BSA, UR144-BSA;
• Cocaine, such as BZEG-BSA;
• Hallucinogens/Anesthetics such as, Ketamine-BSA and PCP-BSA;
• Nicotinic such as, Cotinine-BSA.
• Opioids such as, Buprenorphine-BSA, Fentanyl-BSA, Methadone-BSA, Morphine-BSA, Oxycodone-BSA, Propoxyphene-BSA and others such as Chloramphenicol-BSA, Gabapentin-BSA and N-acetyl glucosamine-BSA (NAG-BSA).

If you would like any more information about our drug conjugates, please do not hesitate to contact us.