We have located links that may give you full text access.
Tumor-Shed Antigen Affects Antibody Tumor Targeting: Comparison of Two 89 Zr-Labeled Antibodies Directed against Shed or Nonshed Antigens.
We investigated the effect of shed antigen mesothelin on the tumor uptake of amatuximab, a therapeutic anti-mesothelin mAb clinically tested in mesothelioma patients. The B3 mAb targeting a nonshed antigen was also analyzed for comparison. The mouse model implanted with A431/H9 tumor, which expresses both shed mesothelin and nonshed Lewis-Y antigen, provided an ideal system to compare the biodistribution and PET imaging profiles of the two mAbs. Our study demonstrated that the tumor and organ uptakes of 89 Zr-B3 were dose-independent when 3 doses, 2, 15, and 60 μ g B3, were compared at 24 h after injection. In contrast, tumor and organ uptakes of 89 Zr-amatuximab were dose-dependent, whereby a high dose (60 μ g) was needed to achieve tumor targeting comparable to the low dose (2 μ g) of 89 Zr-B3, suggesting that shed mesothelin may affect amatuximab tumor targeting as well as serum half-life. The autoradiography analysis showed that the distribution of 89 Zr-B3 was nonuniform with the radioactivity primarily localized at the tumor periphery independent of the B3 dose. However, the autoradiography analysis for 89 Zr-amatuximab showed dose-dependent distribution profiles of the radiolabel; at 10 μ g dose, the radiolabel penetrated toward the tumor core with its activity comparable to that at the tumor periphery, whereas at 60 μ g dose, the distribution profile became similar to those of 89 Zr-B3. These results suggest that shed antigen in blood may act as a decoy requiring higher doses of mAb to improve serum half-life as well as tumor targeting. Systemic mAb concentration should be at a severalfold molar excess to the shed Ag in blood to overcome the hepatic processing of mAb-Ag complexes. On the other hand, mAb concentration should remain lower than the shed Ag concentration in the tumor ECS to maximize tumor penetration by passing binding site barriers.
Full text links
Related Resources
Trending Papers
Executive Summary: State-of-the-Art Review: Unintended Consequences: Risk of Opportunistic Infections Associated with Long-term Glucocorticoid Therapies in Adults.Clinical Infectious Diseases 2024 April 11
Autoimmune Hemolytic Anemias: Classifications, Pathophysiology, Diagnoses and Management.International Journal of Molecular Sciences 2024 April 13
Clinical practice guidelines on the management of status epilepticus in adults: A systematic review.Epilepsia 2024 April 13
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app