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

MR Parkhurst, JC Yang, RC Langan, ME Dudley… - Molecular Therapy, 2011 - cell.com
MR Parkhurst, JC Yang, RC Langan, ME Dudley, DAN Nathan, SA Feldman, JL Davis
Molecular Therapy, 2011cell.com
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 …
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.
cell.com