Explore Antibody Drug Conjugates

Combining the selectivity of monoclonal antibodies with highly potent cytotoxic agents

Building on the potential of monoclonal antibodies, an established pillar of cancer treatment, antibody drug conjugates (ADCs) combine the power of chemotherapy with the selectivity of monoclonal antibodies.1 Through experience in the promising area of ADC development, Genentech seeks to identify novel targets and to further advance a new generation of ADCs.

ADC technology potentially allows for selective intervention with a potent cytotoxic agent, which is often too toxic to be given as conventional chemotherapy, by linking it to a target-specific monoclonal antibody. This molecular structure is designed to maximize chemotherapy delivery and its release inside the tumor cell, while minimizing the exposure of healthy cells to the toxin.2

 

Antibody drug conjugates are constructed of a monoclonal antibody, stable linker, and highly potent cytotoxin Antibody drug conjugates are constructed of a monoclonal antibody, stable linker, and highly potent cytotoxin

 

ADC development is dependent on the selection of an appropriate target tumor antigen.2  Genentech is investigating novel targets, such as CD79b, which are expressed on nearly all malignant B cells.3,4

ADCs are designed to selectively bind to target antigens, triggering internalization by the cell. Once internalized and trafficked within the lysosome, the stable linker is cleaved, releasing the cytotoxic agent, and potentially leading to apoptosis.2,3

Genentech is currently investigating the potential of using an ADC with other agents, such as traditional monoclonal antibodies, PD-L1 inhibitors, small molecules, and T-cell bispecific antibodies.

References

  1. Diamantis N, Banerji U. Antibody-drug conjugates—an emerging class of cancer treatment. Br J Cancer. 2016;114:362-367. PMID: 26742008
  2. Peters C, Brown S. Antibody–drug conjugates as novel anti-cancer chemotherapeutics. Biosci Rep. 2015;35. pii: e00225. PMID: 26182432
  3. Polson AG, Yu S-F, Elkins K, et al. Antibody-drug conjugates targeted to CD79 for the treatment of non-Hodgkin lymphoma. Blood. 2007;110:616-623. PMID: 17374736
  4. Types of non-Hodgkin lymphoma. American Cancer Society. http://www.cancer.org/cancer/non-hodgkinlymphoma/detailedguide/non-hodgkin-lymphoma-types-of-non-hodgkin-lymphoma. Accessed February 10, 2018.