GUCY2C-targeted cancer immunotherapy: past, present and future

Immunol Res. 2011 Dec;51(2-3):161-9. doi: 10.1007/s12026-011-8253-7.


For the last decade, we have focused on guanylyl cyclase C (GUCY2C) as a potentially ideal target antigen for colorectal cancer immunotherapy. GUCY2C is expressed only in intestinal epithelial cells and by nearly 100% of colorectal cancers. We have developed and tested a recombinant adenoviral vector possessing GUCY2C (Ad5-GUCY2C) as a candidate vaccine for colorectal cancer patients. Murine studies have revealed that this vaccine is safe and effective against GUCY2C-expressing targets, and Ad5-GUCY2C is poised for phase I clinical testing in colorectal cancer patients with minimal residual disease. Moreover, we are developing second-generation GUCY2C-targeted therapeutics, including the use of chimeric antigen receptor (CAR)-expressing T cells, for treatment of patients with advanced colorectal cancer for whom Ad5-GUCY2C immunization is not appropriate. Thus, a family of GUCY2C-targeted immunotherapeutics may bridge the gap in effective treatments for the 500,000 patients worldwide who die annually from colorectal cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / immunology
  • Adenocarcinoma / therapy*
  • Adenoviridae / genetics
  • Animals
  • Clinical Trials as Topic
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / immunology
  • Colorectal Neoplasms / therapy*
  • Genetic Vectors
  • Humans
  • Immunotherapy / methods*
  • Mice
  • Molecular Targeted Therapy / methods*
  • Receptors, Enterotoxin
  • Receptors, Guanylate Cyclase-Coupled / genetics
  • Receptors, Guanylate Cyclase-Coupled / immunology
  • Receptors, Guanylate Cyclase-Coupled / metabolism*
  • Receptors, Peptide / genetics
  • Receptors, Peptide / immunology
  • Receptors, Peptide / metabolism*


  • Receptors, Peptide
  • GUCY2C protein, human
  • Gucy2c protein, mouse
  • Receptors, Enterotoxin
  • Receptors, Guanylate Cyclase-Coupled