A short history of Antibody-Drug Conjugates (ADC) development

The concept of drug targeting has been attributed to paul Ehrlich who conceived the "magic bullet" idea in the year 900. The development of this idea, particularly for cancer treatment, had to wait until the 1970`s. The first studies of using antibodies as carriers for cytotoxic drugs was introduced mainly by our group¹. I tried to call it affinity therapy but for "unknown" reasons it was changed to "immunotoxins" and finally to antibody-drug conjugates (ADC). We found that conjugation by reversable bonds which releases the drug was better than non reversable bonds and the best was a mixture of the specific antibody with the cytotoxic drug².

The field of ADC continued to develope with the advancement of conjugation chemistry, immunology and molecular biology. Three ADC`s received in the recent year marketing authorization from the FDA for treating Hodgkin Lymphoma, Anaplastic Large Cell Lymphoma and HER2 positive Breast Cancer.

This stimulated many companies to enter the field and currently there are more than 6- ADC`s in clinical evaluation³.

1. Hurwitz E, Levy R, Maron R, Wichek M, Arnon R, Sela M, (1975) The convalent binding of daunomycin and adriamycin to antibodies with retention of both drug and antibody activities, Cancer Res 35:1175-1181
2. Hurwitz E, Maron R, Bernstein A, Wichek M, Sela M, Arnon R (1978) The effect in vivo of chemotheraputic drug antibody conjugates in two murine experimental tumor systems , Intl. J. Cancer 21:747-755
3. Lambert G M, Morris C Q (2017) Antibody-drug conjugates (ADC`s) for personalized treatment of solid tumors: A review, Adv. Ther 34:1015-1035