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| PHARMACOKINETICS AND IMMUNE-RESPONSE OF I-131 CHIMERIC MOUSE HUMAN-B72.3 (HUMAN LAMBDA-4) MONOCLONAL-ANTIBODY IN HUMANS |
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| Author(s): KHAZAELI MB, SALEH MN, LIU TP, MEREDITH RF, WHEELER RH, BAKER TS, KING D, SECHER D, ALLEN L, ROGERS K, COLCHER D, SCHLOM J, SHOCHAT D, LOBUGLIO AF |
| Source: CANCER RESEARCH Volume: 51 Issue: 20 Pages: 5461-5466 Published: OCT 15 1991 |
| Times Cited: 139 References: 31 |
| Abstract: Chimeric B72.3, composed of the V-regions of murine B72.3 and the constant regions of human immunoglobulin G4 heavy and kappa-light chain, was administered as a I-131-labeled conjugate to 12 patients with metastatic colon cancer. Seven of these patients had an antibody response after initial infusion, and the immune response was primarily directed to the murine V-region, although a small proportion of the antibody response was directed to topographical epitopes requiring the presence of both murine V-region and human CH-1 and kappa-constant regions (neo-epitopes). The pharmacokinetics included a plasma disappearance curve best fit by a two-compartmental model with an alpha t1/2 of 18 +/- 7 h and a beta-t1/2 of 224 +/- 66 h. A second infusion of the same dose of I-131-chimeric B72.3 was administered to four of these patients 8 wk after the first infusion. Two patients who had a high antibody response to initial infusion had an anamnestic antibody response, and the infused ch-B72.3 rapidly disappeared from the circulation with associated immune complexes and free I-131 in the plasma. One patient with no initial antibody response had no antibody response and identical pharmacokinetics on second infusion. One patient with a modest transient antibody response to initial infusion had no antibody response on second infusion and a modest shortening of plasma circulation. Thus, the human immunoglobulin G4 isotype chimeric B72.3 monoclonal antibody has a plasma half-life 6 to 8 times as long as murine B72.3 and retains considerable immunogenicity in some patients which can adversely affect repetitive infusions. |
| Document Type: Article |
| Language: English |
| Reprint Address: KHAZAELI, MB (reprint author), UNIV ALABAMA, CTR COMPREHENS CANC, LB WALLACE TUMOR INST 262B, UAB STN, BIRMINGHAM, AL 35294 USA |
Addresses:
1. VET ADM MED CTR, BIRMINGHAM, AL 35233 USA
2. CELLTECH LTD, SLOUGH, ENGLAND
3. NCI, BETHESDA, MD 20892 USA
4. AMER CYANAMID CO, PEARL RIVER, NY 10965 USA |
| Publisher: AMER ASSOC CANCER RESEARCH, PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 |
| Subject Category: Oncology |
| IDS Number: GJ908 |
| ISSN: 0008-5472 |
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