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Research ADCs

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Monoclonal antibody

Monoclonal antibodies are designed to target cancer cells specifically and may exhibit their own anticancer effects1-5

A monoclonal antibody targets antigens that are preferentially or exclusively expressed on the surface of cancer cells. Monoclonal antibodies incorporated into ADCs may also retain the anticancer properties of the unconjugated monoclonal antibody.1-5

In addition, a monoclonal antibody may persist in circulation for long periods of time to allow for prolonged exposure of the ADC to the cancer cells.5 Monoclonal antibodies that are components of an ADC may be internalized upon binding to their target antigen, which ultimately allows them to deliver the cytotoxic specifically to target tumor cells.1,5,6

Monoclonal antibody

  • The first step toward successful development of an ADC is a comprehensive understanding of the cancer biology and the identification of the proper target antigen for the cancer1,3,4
  • Once this target for the cancer type is chosen, a monoclonal antibody may be engineered for it1
  • Monoclonal antibodies that exhibit anticancer activities may retain these activities when integrated into an ADC4
  • Preclinical studies show that these anticancer activities may include prevention of signaling, ability to initiate a cytotoxic immune response (eg, antibody-dependent cellular cytotoxicity [ADCC]), and induction of apoptosis4

Components of ADCs currently under investigation: targeted monoclonal antibodies

Target antigen* Cancer type
CD207 B-cell lymphoma, NHL
HER28 HER2-positive breast cancer
EGFR9 Colorectal cancer, head and neck cancer
VEGF-A10 Colorectal cancer, lung, kidney, glioblastoma
CD5211 B-cell lymphoma
CD13812 Multiple myeloma
CD2213 NHL
EphA28 Solid tumors
AGS-514 Pancreatic cancer, prostate cancer, epithelial tumors
Nectin-414 Bladder, breast, lung, and pancreatic
GPMNB8 Breast cancer, melanoma
CD7411 Multiple myeloma
Le11 Prostate cancer, ovarian cancer
CD1914 NHL
*This is not a complete list of target antigens under investigation in ADCs.
References:
1.
Jaracz S, Chen J, Kuznetsova LV, Ojima I. Recent advances in tumor-targeting anticancer drug conjugates. Bioorg Med Chem. 2005;13:5043-5054.
2.
Ricart AD, Tolcher AW. Technology insight: cytotoxic drug immunoconjugates for cancer therapy. Nat Clin Pract Oncol. 2007;4:245-255.
3.
Carter PJ, Senter PD. Antibody-drug conjugates for cancer therapy. Cancer J. 2008;14:154-169.
4.
Oflazoglu E, Stone IJ, Gordon K, et al. Potent anticarcinoma activity of the humanized anti-CD70 antibody h1F6 conjugated to the tubulin inhibitor auristatin via an uncleavable linker. Clin Cancer Res. 2008;14:6171-6180.
5.
Chari RVJ. Targeted cancer therapy: conferring specificity to cytotoxic drugs. Acc Chem Res. 2008;41:98-107.
6.
Sanderson RJ, Hering MA, James SF, et al. In vivo drug-linker stability of an anti-CD30 dipeptide-linked auristatin immunoconjugate. Clin Cancer Res. 2005;11:843-852.
7.
Teicher BA. Antibody-drug conjugate targets. Curr Cancer Drug Targets. 2009;9:982-1004.
8.
Alley SC, Okeley NM, Senter PD. Antibody-drug conjugates: targeted drug delivery for cancer. Current Opin Chem Biol. 2010;14:529-537.
9.
ERBITUX® (cetuximab) Prescribing Information. 2011.
10.
National Cancer Institute website. http://www.cancer.gov/cancertopics/druginfo. Accessed October 24, 2011.
11.
US National Institutes of Health. ClinicalTrials.gov website. www.clinicaltrials.gov. Accessed October 26, 2011.
12.
Beck A, Senter P, Chari R. World Antibody Drug Conjugate Summit Europe: February 21-23, 2011; Frankfurt, Germany. MAbs. 2011;3:331-337.
13.
Fayad L, Patel H, Verhoef G, et al. Blood. 2008;112(11). Abstract 266.
14.
Seattle Genetics website. Product pipeline. http://www.seagen.com/product_pipeline.php. Accessed October 24, 2011.