T Cells Targeting Carcinoembryonic Antigen Can Mediate Regression of Metastatic Colorectal Cancer but Induce Severe Transient Colitis

Mol Ther. 2011 Mar;19(3):620-6. doi: 10.1038/mt.2010.272. Epub 2010 Dec 14.

Abstract

Autologous T lymphocytes genetically engineered to express a murine T cell receptor (TCR) against human carcinoembryonic antigen (CEA) were administered to three patients with metastatic colorectal cancer refractory to standard treatments. All patients experienced profound decreases in serum CEA levels (74-99%), and one patient had an objective regression of cancer metastatic to the lung and liver. However, a severe transient inflammatory colitis that represented a dose limiting toxicity was induced in all three patients. This report represents the first example of objective regression of metastatic colorectal cancer mediated by adoptive T cell transfer and illustrates the successful use of a TCR, raised in human leukocyte antigen (HLA) transgenic mice, against a human tumor associated antigen. It also emphasizes the destructive power of small numbers of highly avid T cells and the limitations of using CEA as a target for cancer immunotherapy.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adult
  • Animals
  • Carcinoembryonic Antigen / blood
  • Carcinoembryonic Antigen / immunology*
  • Colitis / chemically induced
  • Colitis / immunology*
  • Colitis / pathology
  • Colorectal Neoplasms / diagnostic imaging
  • Colorectal Neoplasms / immunology*
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / secondary*
  • Colorectal Neoplasms / therapy
  • Gene Transfer Techniques
  • Genetic Vectors / genetics
  • Genetic Vectors / metabolism
  • Humans
  • Immunotherapy, Adoptive
  • Male
  • Mice
  • Middle Aged
  • Radiography
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / immunology*
  • Receptors, Antigen, T-Cell / metabolism
  • Retroviridae / genetics
  • Retroviridae / metabolism
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Treatment Outcome

Substances

  • Carcinoembryonic Antigen
  • Receptors, Antigen, T-Cell