Title |
Targeting the T cell receptor β-chain constant region for immunotherapy of T cell malignancies
|
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Published in |
Nature Medicine, November 2017
|
DOI | 10.1038/nm.4444 |
Pubmed ID | |
Authors |
Paul M Maciocia, Patrycja A Wawrzyniecka, Brian Philip, Ida Ricciardelli, Ayse U Akarca, Shimobi C Onuoha, Mateusz Legut, David K Cole, Andrew K Sewell, Giuseppe Gritti, Joan Somja, Miguel A Piris, Karl S Peggs, David C Linch, Teresa Marafioti, Martin A Pule |
Abstract |
Mature T cell cancers are typically aggressive, treatment resistant and associated with poor prognosis. Clinical application of immunotherapeutic approaches has been limited by a lack of target antigens that discriminate malignant from healthy (normal) T cells. Unlike B cell depletion, pan-T cell aplasia is prohibitively toxic. We report a new targeting strategy based on the mutually exclusive expression of T cell receptor β-chain constant domains 1 and 2 (TRBC1 and TRBC2). We identify an antibody with unique TRBC1 specificity and use it to demonstrate that normal and virus-specific T cell populations contain both TRBC1(+) and TRBC2(+) compartments, whereas malignancies are restricted to only one. As proof of concept for anti-TRBC immunotherapy, we developed anti-TRBC1 chimeric antigen receptor (CAR) T cells, which recognized and killed normal and malignant TRBC1(+), but not TRBC2(+), T cells in vitro and in a disseminated mouse model of leukemia. Unlike nonselective approaches targeting the entire T cell population, TRBC-targeted immunotherapy could eradicate a T cell malignancy while preserving sufficient normal T cells to maintain cellular immunity. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 26 | 16% |
United Kingdom | 18 | 11% |
Spain | 11 | 7% |
Australia | 3 | 2% |
Japan | 3 | 2% |
Germany | 3 | 2% |
Switzerland | 3 | 2% |
Sweden | 2 | 1% |
Canada | 2 | 1% |
Other | 20 | 13% |
Unknown | 68 | 43% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 103 | 65% |
Scientists | 40 | 25% |
Practitioners (doctors, other healthcare professionals) | 10 | 6% |
Science communicators (journalists, bloggers, editors) | 6 | 4% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 312 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 71 | 23% |
Student > Ph. D. Student | 46 | 15% |
Other | 27 | 9% |
Student > Doctoral Student | 23 | 7% |
Student > Bachelor | 21 | 7% |
Other | 51 | 16% |
Unknown | 73 | 23% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 66 | 21% |
Biochemistry, Genetics and Molecular Biology | 50 | 16% |
Agricultural and Biological Sciences | 43 | 14% |
Immunology and Microbiology | 39 | 13% |
Pharmacology, Toxicology and Pharmaceutical Science | 8 | 3% |
Other | 31 | 10% |
Unknown | 75 | 24% |