Fifty Years of Monoclonals: from hybridomas to next generation antibody therapeutics

Listen in to The Antibody Society's December 4, 2025 webinar featuring Dr. Paul Carter as he covers the history of monoclonal technologies from the first hybridomas in 1975 to the more than 200 approved antibody therapeutics that are saving the lives of millions of patients. Note: the audio is a bit rough, at least when I listened to it.

Dr. Carter is a Genentech Fellow in the Antibody Engineering Department and he starts his review with Köhler and Milstein's Nature publication on August 7, 1975. This publication detailed the way in which hybridoma technology enabled a stable and unending source of selective target monoclonal antibodies. This was the first and critical step towards using antibodies as a therapeutic given that they had to be easily and stably available for research, development, and administration to patients. From this initial work there have been over 15,800 US patents issued, as detailed in Carter's recent publication in Nature Reviews Immunology, October 2025.

It took 11 years for the first approved antibody therapeutic, but it took until the 2000s for the field to really take off.  There are many reasons for this slow path--the targets had to be found, making antibodies on a pharmaceutical scale had never been done before, and murine (mouse) antibodies had drawbacks in humans. Overcoming the murine shortcomings was done by humanization-swapping out domains until the antibodies are well tolerated in humans. At present, most therapies are based on human antibodies or humanized antibodies. 

Dr Carter made a very interesting statement shortly after the 14 minute mark. He said that the unsung hero of this field was biomanufacturing. He recognized the immense innovation needed to go from the research lab scale to the biomanufacturing scale production of antibodies.  It was great to hear biomanufacturing get acknowledged like that!

Next, Dr. Carter reviewed the various technologies being used to design the therapeutics--the rise of bispecific antibodies and antibody-drug conjugates (ADCs), although traditional IgG based treatments still dominate in numbers. In addition, the development of CAR T-cell treatments has added another, powerful option in the fight against disease. 

Dr Carter briefly covered administration methods. Currently, intravenous treatments dominated with the second most frequent category being subcutaneous, although there are still challenges with this desirable and convenient delivery method.

One of the most amazing treatments are those that were developed to target breast cancer, specifically HER2+ tumors. Dr Carter walks through the evolution of those treatments, and then moves to discuss B-cell lineage marker targeted treatments. The nomenclature becomes intense, but the message is clear--antibody therapeutics are an incredible addition to fighting disease. And Dr. Carter does not shy away from mentioning treatments that were withdrawn from the market--its important to learn from failures as well as successes!

Finally, Dr. Carter discusses the future of antibody therapeutics, with a realization that there are so many other ways they can be designed (AI?), delivered, and targeted.

Overall, an excellent and entertaining review of a very important field!