| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Department of Clinical Immunology and
Department of Protein Science, Amgen, Thousand Oaks, CA 91320
Evaluation of the immunogenicity of panitumumab, a fully human anti-epidermal growth factor receptor mAb approved for use in colorectal cancer patients, led to the development of two separate immunoassays for the detection of anti-panitumumab Abs. The first immunoassay used a bridging ELISA capable of detecting 10 ng/ml positive control anti-panitumumab Ab. The ELISA incorporated an acid dissociation step to reduce drug interference and tolerated the presence of 
100-fold molar excess of drug. During eight clinical trials, the ELISA detected developing Ab responses in 2 of 612 (0.3%) subjects. In one of the ELISA positive subjects, neutralizing Abs were detected using an epidermal growth factor receptor phosphorylation bioassay. The second immunoassay used a Biacore biosensor immunoassay format capable of detecting 1 µg/ml positive control Ab while tolerating the presence of equal molar amounts of drug. Although less sensitive and less tolerant to competing drug in the assay, the Biacore assay detected developing Ab responses in 25 of the 604 (4.1%) subjects. Additionally, the Biacore assay identified eight subjects who developed neutralizing Abs. Mouse mAbs with affinities ranging from 1.1 x 10–6 to 8.4 x 10–10 M were used to characterize both assay types. The ELISA was more sensitive for the detection of higher affinity mAbs and detected high-affinity mAbs in the presence of higher molar ratio of drug to mAb. The Biacore assay was more sensitive for detection of lower affinity mAbs and detected low affinity Abs in the presence of higher molar ratios of drug to mAb.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 Address correspondence and reprint requests to Dr. Michael C. Mullenix, Department of Clinical Immunology, One Amgen Center Drive, Thousand Oaks, CA 91320. E-mail address: mullenix{at}amgen.com
2 Abbreviations used in this paper: EGFR, epidermal growth factor receptor; DPBS, Dulbecco’s PBS; RU, response unit.
This article has been cited by other articles:
|
|
 |
|
  P. Ma, B.-B. Yang, Y.-M. Wang, M. Peterson, A. Narayanan, L. Sutjandra, R. Rodriguez, and A. Chow Population Pharmacokinetic Analysis of Panitumumab in Patients With Advanced Solid Tumors J. Clin. Pharmacol., October 1, 2009; 49(10): 1142 - 1156. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. I. AVRAMIS, E. V. AVRAMIS, W. HUNTER, and M. C. LONG Immunogenicity of Native or Pegylated E. coli and Erwinia Asparaginases Assessed by ELISA and Surface Plasmon Resonance (SPR-Biacore) Assays of IgG Antibodies (Ab) in Sera from Patients with Acute Lymphoblastic Leukemia (ALL) Anticancer Res, January 1, 2009; 29(1): 299 - 302. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Van Cutsem, S. Siena, Y. Humblet, J.-L. Canon, J. Maurel, E. Bajetta, B. Neyns, D. Kotasek, A. Santoro, W. Scheithauer, et al. An open-label, single-arm study assessing safety and efficacy of panitumumab in patients with metastatic colorectal cancer refractory to standard chemotherapy Ann. Onc., January 1, 2008; 19(1): 92 - 98. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
