GUCY2C-targeted cancer immunotherapy: past, present and future.
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.
Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, 1020 Locust Street, JAH 348A, Philadelphia, PA 19107, USA. Adam.Snook@jefferson.edu
Adam E
AE
Snook
Michael S
MS
Magee
Scott A
SA
Waldman
D000230:Adenocarcinoma / Q000188:drug therapy / Q000276:immunology / Q000628:therapy*; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002986:Clinical Trials as Topic; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000628:therapy*; D005822:Genetic Vectors; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D051379:Mice; D058990:Molecular Targeted Therapy / Q000379:methods*; D000074261:Receptors, Enterotoxin; D050705:Receptors, Guanylate Cyclase-Coupled / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D018000:Receptors, Peptide / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D018000:Receptors, Peptide; C000613654:GUCY2C protein, human; C000613655:Gucy2c protein, mouse; D000074261:Receptors, Enterotoxin; D050705:Receptors, Guanylate Cyclase-Coupled