T cells targeting carcinoembryonic antigen can mediate regression of metastatic colorectal cancer but induce severe transient colitis

Maria R. Parkhurst, James C. Yang, Russell C. Langan, Mark E. Dudley, Debbie Ann N. Nathan, Steven A. Feldman, Jeremy L. Davis, Richard A. Morgan, Maria J. Merino, Richard M. Sherry, Marybeth S. Hughes, Udai S. Kammula, Giao Q. Phan, Ramona M. Lim, Stephen A. Wank, Nicholas P. Restifo, Paul F. Robbins, Carolyn M. Laurencot, Steven A. Rosenberg

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)620-626
Number of pages7
JournalMolecular Therapy
Volume19
Issue number3
DOIs
StatePublished - Mar 2011
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

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