| Chapter title |
Pharmacology of anti-CD3 diphtheria immunotoxin in CD3 positive T-cell lymphoma trials.
|
|---|---|
| Chapter number | 10 |
| Book title |
Immunotherapy of Cancer
|
| Published in |
Methods in molecular biology, January 2010
|
| DOI | 10.1007/978-1-60761-786-0_10 |
| Pubmed ID | |
| Book ISBNs |
978-1-60761-785-3, 978-1-60761-786-0
|
| Authors |
Jung Hee Woo, Yu-Jen Lee, David M. Neville, Arthur E. Frankel, Woo, Jung Hee, Lee, Yu-Jen, Neville, David M., Frankel, Arthur E. |
| Abstract |
Anti-CD3 recombinant diphtheria immunotoxin, A-dmDT(390)-bisFv(UCHT1), consists of the catalytic and translocation domains of diphtheria toxin fused to two single chain Fv fragments of an anti-CD3epsilon monoclonal antibody (UCHT1). A-dmDT(390)-bisFv(UCHT1) is capable of killing CD3(+) T-lymphoma cells and normal T cells specifically in the femtomolar concentration range. To study pharmacology of A-dmDT(390)-bisFv(UCHT1) in patients with CD3(+) T-cell lymphoma in a phase I clinical trial, (1) highly sensitive bioassay using Jurkat cells for measuring drug levels, (2) ELISA for measuring anti-DT antibody titer, and (3) 5-color FACS analysis method for measuring changes of subtype T-cell population were developed. In addition to evaluating drug efficacy and pharmacokinetics in patients, it is important to correlate pre-existing anti-DT antibody levels with maximum drug concentration in serum and extent of T-cell depletion because pre-existing anti-DT antibodies due to DPT (Diphtheria, Pertussis, and Tetanus) immunization can neutralize diphtheria immunotoxin. We observed that at the lowest treatment dose (2.5 microg/kg: twice daily for 4 days) A-dmDT(390)-bisFv(UCHT1) depletes greater than 99.0% of normal T cells in all six patients for a short period of time (2-3 days) and that there is no association of C (max) and extent of T-cell depletion with the pre-existing anti-DT antibody titer. |
Mendeley readers
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 11 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Master | 3 | 27% |
| Professor | 2 | 18% |
| Student > Ph. D. Student | 2 | 18% |
| Student > Bachelor | 1 | 9% |
| Researcher | 1 | 9% |
| Other | 1 | 9% |
| Unknown | 1 | 9% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 6 | 55% |
| Medicine and Dentistry | 2 | 18% |
| Chemistry | 1 | 9% |
| Biochemistry, Genetics and Molecular Biology | 1 | 9% |
| Unknown | 1 | 9% |