title: T cells targeting carcinoembryonic antigen can mediate regression of metastatic colorectal cancer but induce severe transient colitis.
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.
authors.affiliation: Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Maria_Parkhurst@nih.gov
authors.forename: Maria R
authors.initials: MR
authors.lastname: Parkhurst
authors.forename: James C
authors.initials: JC
authors.lastname: Yang
authors.forename: Russell C
authors.initials: RC
authors.lastname: Langan
authors.forename: Mark E
authors.initials: ME
authors.lastname: Dudley
authors.forename: Debbie-Ann N
authors.initials: DA
authors.lastname: Nathan
authors.forename: Steven A
authors.initials: SA
authors.lastname: Feldman
authors.forename: Jeremy L
authors.initials: JL
authors.lastname: Davis
authors.forename: Richard A
authors.initials: RA
authors.lastname: Morgan
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Merino
authors.forename: Richard M
authors.initials: RM
authors.lastname: Sherry
authors.forename: Marybeth S
authors.initials: MS
authors.lastname: Hughes
authors.forename: Udai S
authors.initials: US
authors.lastname: Kammula
authors.forename: Giao Q
authors.initials: GQ
authors.lastname: Phan
authors.forename: Ramona M
authors.initials: RM
authors.lastname: Lim
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Wank
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Restifo
authors.forename: Paul F
authors.initials: PF
authors.lastname: Robbins
authors.forename: Carolyn M
authors.initials: CM
authors.lastname: Laurencot
authors.forename: Steven A
authors.initials: SA
authors.lastname: Rosenberg
mesh_terms: D000328:Adult; D000818:Animals; D002272:Carcinoembryonic Antigen / Q000097:blood / Q000276:immunology*; D003092:Colitis / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000000981:diagnostic imaging / Q000276:immunology* / Q000473:pathology / Q000556:secondary* / Q000628:therapy; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D016219:Immunotherapy, Adoptive; D008297:Male; D051379:Mice; D008875:Middle Aged; D011859:Radiography; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D002272:Carcinoembryonic Antigen; D011948:Receptors, Antigen, T-Cell