Abstract
Anti-CD3 monoclonal antibodies induce the proliferation of human T-cells in vitro and activate specific and nonspecific cytolysis by human T-cell clones and human peripheral blood lymphocytes. In vivo administration of anti-CD3 prevents tumor growth of a UV-induced mouse fibrosarcoma. We conducted a phase I trial to determine the toxicity and immunomodulatory properties of low doses of anti-CD3 in 36 patients with cancer. In 23 patients, anti-CD3 was given i.v. over 3 h at 1,10,30, and 100 meg/patient. Five other patients received anti-CD3 at 30 meg by i.v. bolus. Patients were treated every 3 days for a total of four doses. An additional eight patients received anti-CD3 daily for 14 days at 3 meg by i.v. bolus, 3-h infusion, or 24-h infusion. Dose-limiting toxicity was headache. Headache was often accompanied by signs and symptoms of meningeal irritation leading to performance of a lumbar puncture in nine patients. The opening pressure was usually elevated, and six patients had a cerebrospinal fluid lymphocytosis with an elevated protein. Increased levels of interleukin 6 were identified in the cerebrospinal fluid. The maximum tolerated dose by 3-h infusion was 30 meg. There were no objective tumor responses. There was a dose-related increase in the number of peripheral blood lymphocytes expressing the T-cell activation antigen CD69 (Leu 23), but no changes were seen in CD25 (interleukin 2 receptor) expression, and no changes were observed in the serum levels of the soluble interleukin 2 receptor. Even at these low doses of anti-CD3,8 of 16 patients tested developed human anti-mouse antibodies.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2394-2401 |
| Number of pages | 8 |
| Journal | Cancer Research |
| Volume | 52 |
| Issue number | 9 |
| State | Published - Jan 1 1992 |
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ASJC Scopus subject areas
- Oncology
- Cancer Research
Cite this
Anti-CD3 Monoclonal Antibody Treatment of Patients with CD3-Negative Tumors : A Phase IA/B Study. / Urba, Walter J.; Ewel, Cynthia; Kopp, William; Rossio, Jeffrey; Beveridge, Joy; Fenton, Robert; Janik, John; Longo, Dan L.; Janik, John Edward.
In: Cancer Research, Vol. 52, No. 9, 01.01.1992, p. 2394-2401.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Anti-CD3 Monoclonal Antibody Treatment of Patients with CD3-Negative Tumors
T2 - A Phase IA/B Study
AU - Urba, Walter J.
AU - Ewel, Cynthia
AU - Kopp, William
AU - Rossio, Jeffrey
AU - Beveridge, Joy
AU - Fenton, Robert
AU - Janik, John
AU - Longo, Dan L.
AU - Janik, John Edward
PY - 1992/1/1
Y1 - 1992/1/1
N2 - Anti-CD3 monoclonal antibodies induce the proliferation of human T-cells in vitro and activate specific and nonspecific cytolysis by human T-cell clones and human peripheral blood lymphocytes. In vivo administration of anti-CD3 prevents tumor growth of a UV-induced mouse fibrosarcoma. We conducted a phase I trial to determine the toxicity and immunomodulatory properties of low doses of anti-CD3 in 36 patients with cancer. In 23 patients, anti-CD3 was given i.v. over 3 h at 1,10,30, and 100 meg/patient. Five other patients received anti-CD3 at 30 meg by i.v. bolus. Patients were treated every 3 days for a total of four doses. An additional eight patients received anti-CD3 daily for 14 days at 3 meg by i.v. bolus, 3-h infusion, or 24-h infusion. Dose-limiting toxicity was headache. Headache was often accompanied by signs and symptoms of meningeal irritation leading to performance of a lumbar puncture in nine patients. The opening pressure was usually elevated, and six patients had a cerebrospinal fluid lymphocytosis with an elevated protein. Increased levels of interleukin 6 were identified in the cerebrospinal fluid. The maximum tolerated dose by 3-h infusion was 30 meg. There were no objective tumor responses. There was a dose-related increase in the number of peripheral blood lymphocytes expressing the T-cell activation antigen CD69 (Leu 23), but no changes were seen in CD25 (interleukin 2 receptor) expression, and no changes were observed in the serum levels of the soluble interleukin 2 receptor. Even at these low doses of anti-CD3,8 of 16 patients tested developed human anti-mouse antibodies.
AB - Anti-CD3 monoclonal antibodies induce the proliferation of human T-cells in vitro and activate specific and nonspecific cytolysis by human T-cell clones and human peripheral blood lymphocytes. In vivo administration of anti-CD3 prevents tumor growth of a UV-induced mouse fibrosarcoma. We conducted a phase I trial to determine the toxicity and immunomodulatory properties of low doses of anti-CD3 in 36 patients with cancer. In 23 patients, anti-CD3 was given i.v. over 3 h at 1,10,30, and 100 meg/patient. Five other patients received anti-CD3 at 30 meg by i.v. bolus. Patients were treated every 3 days for a total of four doses. An additional eight patients received anti-CD3 daily for 14 days at 3 meg by i.v. bolus, 3-h infusion, or 24-h infusion. Dose-limiting toxicity was headache. Headache was often accompanied by signs and symptoms of meningeal irritation leading to performance of a lumbar puncture in nine patients. The opening pressure was usually elevated, and six patients had a cerebrospinal fluid lymphocytosis with an elevated protein. Increased levels of interleukin 6 were identified in the cerebrospinal fluid. The maximum tolerated dose by 3-h infusion was 30 meg. There were no objective tumor responses. There was a dose-related increase in the number of peripheral blood lymphocytes expressing the T-cell activation antigen CD69 (Leu 23), but no changes were seen in CD25 (interleukin 2 receptor) expression, and no changes were observed in the serum levels of the soluble interleukin 2 receptor. Even at these low doses of anti-CD3,8 of 16 patients tested developed human anti-mouse antibodies.
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UR - http://www.scopus.com/inward/citedby.url?scp=0026663524&partnerID=8YFLogxK
M3 - Article
C2 - 1533172
AN - SCOPUS:0026663524
VL - 52
SP - 2394
EP - 2401
JO - Cancer Research
JF - Cancer Research
SN - 0008-5472
IS - 9
ER -