In the field of tumor therapy, antibody-drug conjugate (ADC) with both targeting and strong activities has gradually become the new focus of the industry due to its excellent performance in many indications, and it is known as "the rising star of tumor therapy".

What is ADC

Traditional ADC drug is composed of antibody, linker, and cytotoxic payload. The mechanism of action (MOA) is that ADC drug specifically recognizes and binds to tumor cell surface antigens through antibody targeting, and then the ADC-antigen complex is internalized by the endocytosis of the cell itself, when the ADC ( is degraded in the lysosome, thereby releasing the cytotoxic load (drug) and exerting its effect.

* Antibody: specifically recognize target cells
* Linker: connect antibody and toxin covalently
* Payload: play a role in killing cells

In simple terms, ADC is a combined therapy of monoclonal antibodies and chemotherapy, which has the selectivity of monoclonal antibodies and the lethality of chemotherapy. After the patient receives treatment, the ADC will enter the body circulation. Once the ADC antibody specifically binds to the surface of the tumor cell, the cell membrane of the tumor cell will sink inward to form an endosome to swallow the ADC, which is also called internalization. The antibody part or linker of ADC is often degraded by some enzymes in the cell, thereby releasing the toxin, and the released toxin begins to work and kill the tumor cell. Different toxins kill cells in different ways, but most toxins function in the nucleus.

It can be seen that ADC can use the extremely high specificity of antibodies to accurately deliver drugs into tumor cells to avoid killing normal cells in the body, thereby reducing adverse reactions during treatment.

With the continuous discovery of various disease targets, the demand for precise treatment of single and multiple targets has increased. Therefore, ADC, with few side effects, has become a research hotspot in the field of tumor treatment.

Global market of ADC products

For the two earlier approved drugs, Kadcyla, jointly developed by Roche and ImmunoGen, is the world's first marketed ADC drug for the treatment of solid tumors, of which the sales from 2013 to 2019 increased from 234 million CHF to 1.393 billion CHF, with 34.6% Compound Annual Growth Rate (CAGR). And Adcetris, launched by Seattle Genetics and Takeda, received increased sales from 43 million USD to 630 million USD in 2011-2019, with an 8-year CAGR of 39.8%.

Overall, the launch of ADCs exploded in the past two years, with three approved in 2019 and 2020, and currently about ten already approved worldwide. According to PR Newswire, the ADC drug market will reach 9.93 billion USD in 2025, with a CAGR of 25.9%.

Compared with the existing therapies, most of the ADC drugs on the market show good efficacy, although the safety needs to be further observed.

ADC preparation technology

The entire pipeline of ADC development roughly composes antibody screening, chemical conjugation, and in vitro/in vivo analysis, which requires sophisticated technologies in that it is an organic combination of targets, antibodies, linkers, toxins, and any part could influence the drug properties.

From birth, maturity, to the outbreak, ADC has gone through a long process. To now, more than 100 companies or research institutions in Europe and the United States are carrying out ADC drug research and development projects.

As an antibody-small molecule drug coupling agent, ADC drugs are in line with the concept of "precision medicine". Breakthroughs are still expected in technological transformation, as the new target development is still challenging and the product efficacy and safety are also worthy of attention.

Author's Bio: 

Creative Biolabs is a leading solution provider of ADC.