What are the ADC drugs?

A brief history of Antibody-Drug Conjugates

ADC (antibody-conjugated drug) is not a new concept. As early as the early 20th century, the Nobel Prize winner in medicine, German scientist Paul Ehrlich, already proposed the concept of ADC and called ADC drugs the "magic bullet". But it continued until the 1950s that the research on ADC drugs improved.

In 1958, Mathe first conjugated an anti-mouse antibody with methotrexate for the treatment of leukemia. Because of the problems of immunogenicity and antibody preparation, progress in ADCs did not go very far until the emergence of monoclonal antibodies in 1975, and later the emergence of humanized antibodies.

In 2000, the first antibody-conjugated drug was approved by the FDA for the treatment of acute myeloid leukemia, but it was limited by issues such as coupling technology, targeting, and effectiveness. Antibody-conjugated drugs are unstable in the blood, and small toxin molecules are released early, resulting in serious toxicity, leading to the withdrawal of the first drug from the market in 2010.

However, the effort paid off. After more than 10 years of precipitation, in 2011, the new antibody-conjugated drug Adcetris was approved by the FDA for the treatment of Hokinson’s lymphoma and systemic anaplastic large cell lymphoma. In 2013, Kadcyla was approved by the FDA for the treatment of HER2-positive breast cancer. The appearance of these two drugs has reignited the enthusiasm for ADC research.

What are Antibody Drug Conjugates in a nutshell?

ADC generally includes three parts, monoclonal antibody drugs targeting specific antigens, drugs with cytotoxins, linkers linking antibodies, and small toxin molecules. This structure gives ADC drugs more advantages, making them not only have the powerful killing effect of traditional small molecule chemotherapy but also have the tumor-targeting properties of antibody drugs.

Among them, the antibody is responsible for finding tumor cells, and the linker allows the antibody to carry out entrainment, bringing toxic small molecules into the tumor cells, and the small molecules are a sharp sword to kill the tumor cells. In addition, there are also antibodies that have anti-tumor efficacy.

Due to the large differences in the design of different ADC drugs, even for different drugs with the same target, the differences in recognition sites, connection sites, linkers, and small molecules connected will cause large differences in drug toxicity. The factors that need to be considered in the design of ADC drugs are the factors that affect drug toxicity, including: