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

By M. Parkhurst, Jie Yang, R. Langan, M. Dudley, Debbie-Ann N. Nathan, S. Feldman, Jeremy L. Davis, R. Morgan, M. Merino, R. Sherry and 9 more. Molecular Therapy, 2011

813 citations recorded by the source corpus.

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.

Subfields: Immunology, Oncology

View Paper: https://www.semanticscholar.org/paper/54465856fd5980ccaf74f7c3f42bcc7ec3818608

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

1. C. June
2. S. Rosenberg
3. Wendell A. Lim
4. N. Restifo

In Oncology

1. C. June
2. Wendell A. Lim
3. S. Rosenberg
4. N. Restifo
5. J. Kochenderfer
6. Jennifer N. Brudno
7. Michel Sadelain

Citations in the corpus

• Treatment of metastatic renal cell carcinoma with CAIX CAR-engineered T cells: clinical evaluation and management of on-target toxicity. (2013, neutral): “10 74/M L (12) IFN (17), Sor (17) Lu, Med, Subpl”
• IL-2: The First Effective Immunotherapy for Human Cancer (2014, background): “The exquisite specificity and sensitivity of the immune system in targeting Ags has resulted in substantial toxicity in normal tissues when target Ags are expressed even in low levels such as carcinoembryonic Ag or ERB-B2 (79, 80).”
• The Principles of Engineering Immune Cells to Treat Cancer (2017, background): “After treating three patients, although anti-tumor activity was observed in one patient, all three patients developed severe inflammatory colitis in the colon, resulting in early termination of the trial due to toxicity (Parkhurst et al., 2011).”