| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Cancer Therapy: Clinical |
Authors' Affiliations: 1 Ludwig Institute for Cancer Research, Melbourne Tumour Biology Branch; Departments of 2 Nuclear Medicine and Centre for PET, 3 Surgery, 4 Anatomical Pathology, and 5 Medical Physics, Austin Hospital, Melbourne, Victoria, Australia and 6 Ludwig Institute for Cancer Research, New York, New York
Requests for reprints: Andrew M. Scott, Tumour Targeting Program, Ludwig Institute for Cancer Research, Level 1, Harold Stokes Building, Austin Hospital, 143-165 Studley Road, Heidelberg, Victoria 3084, Australia. Phone: 61-3-9496-5876; Fax: 61-3-9496-5892; E-mail: andrew.scott{at}ludwig.edu.au.
Purpose: To determine the in vivo characteristics of huA33, a CDR-grafted humanized antibody against the A33 antigen, we have conducted an open-label, dose escalation, biopsy-based phase I trial of huA33 in patients with colorectal carcinoma.
Experimental Design: Patients with colorectal carcinoma were infused with [131I]huA33 (400 MBq: 10 mCi) and [125I]huA33 (40 MBq: 1 mCi) 1 week before surgery. There were four huA33 dose levels (0.25, 1.0, 5.0, and 10 mg/m2). Adverse events, pharmacokinetics, biodistribution, tumor biopsies, and immune responses to huA33 were evaluated.
Results: There were 12 patients entered into the trial (6 males and 6 females; age range, 39-66 years). No dose-limiting toxicity was observed. The biodistribution of huA33 showed excellent uptake of [131I]huA33 in metastatic colorectal carcinoma. Pharmacokinetic analysis showed no significant difference in terminal half-life (T1/2ß) between dose levels (mean ± SD, 86.92 ± 22.12 hours). Modeling of colon uptake of huA33 showed a T1/2 of elimination of 32.4 ± 8.1 hours. Quantitative tumor uptake ranged from 2.1 x 10–3 to 11.1 x 10–3 %ID/g, and tumor/normal tissue and tumor/serum ratios reached as high as 16.3:1 and 4.5:1, respectively. Biosensor analysis detected low-level human anti-human antibody responses in four patients following huA33 infusion.
Conclusions: huA33 shows selective and rapid localization to colorectal carcinoma in vivo and penetrates to the center of large necrotic tumors, and colon elimination half-life of huA33 is equivalent to basal colonocyte turnover. The excellent targeting characteristics of this humanized antibody indicate potential for the targeted therapy of metastatic colorectal cancer in future trials.
This article has been cited by other articles:
|
|
 |
|
  M. E. Ackerman, D. Pawlowski, and K. D. Wittrup Effect of antigen turnover rate and expression level on antibody penetration into tumor spheroids Mol. Cancer Ther., July 1, 2008; 7(7): 2233 - 2240. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Koslowski, U. Sahin, K. Dhaene, C. Huber, and O. Tureci MS4A12 Is a Colon-Selective Store-Operated Calcium Channel Promoting Malignant Cell Processes Cancer Res., May 1, 2008; 68(9): 3458 - 3466. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. P. Kelly, F. T. Lee, K. Tahtis, F. E. Smyth, M. W. Brechbiel, and A. M. Scott Radioimmunotherapy with {alpha}-Particle Emitting 213Bi-C-Functionalized trans-Cyclohexyl-Diethylenetriaminepentaacetic Acid-Humanized 3S193 Is Enhanced by Combination with Paclitaxel Chemotherapy Clin. Cancer Res., September 15, 2007; 13(18): 5604s - 5612s. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Scott, N. Tebbutt, F.-T. Lee, T. Cavicchiolo, Z. Liu, S. Gill, A. M.T. Poon, W. Hopkins, F. E. Smyth, C. Murone, et al. A Phase I Biodistribution and Pharmacokinetic Trial of Humanized Monoclonal Antibody Hu3s193 in Patients with Advanced Epithelial Cancers that Express the Lewis-Y Antigen Clin. Cancer Res., June 1, 2007; 13(11): 3286 - 3292. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Scott, F.-T. Lee, N. Tebbutt, R. Herbertson, S. S. Gill, Z. Liu, E. Skrinos, C. Murone, T. H. Saunder, B. Chappell, et al. A phase I clinical trial with monoclonal antibody ch806 targeting transitional state and mutant epidermal growth factor receptors PNAS, March 6, 2007; 104(10): 4071 - 4076. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. M. Bertagnolli Radioimmunotherapy for Colorectal Cancer Clin. Cancer Res., July 1, 2005; 11(13): 4637 - 4638. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
