This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Langmuir, V. K. Articles by Woo, D. V. Search for Related Content PubMed PubMed Citation Articles by Langmuir, V. K. Articles by Woo, D. V.

Comparisons between Two Monoclonal Antibodies That Bind to the Same Antigen but Have Differing Affinities: Uptake Kinetics and ¹²⁵I-Antibody Therapy Efficacy in Multicell Spheroids¹

SRI International, Menlo Park, California 94025 [V. K. L., H. L. M.], and Centocor, Malvern, Pennsylvania 19355 [D. V. W.]

It has been predicted that low affinity antibodies (Abs) should penetrate into tumors more readily than high affinity Abs. However, the absolute uptake and residence time of a high affinity Ab may be better. It is, therefore, not clear whether a high affinity Ab would have a therapeutic advantage. This is particularly relevant with ¹²⁵I radioimmunotherapy, where targeting of every cell is important.

This study compared the uptake kinetics and toxicity in multicell spheroids of two murine monoclonal Abs labeled with ¹²⁵I. 17-1A was produced by immunization with a human colon cancer cell line and has an affinity of 5.15 x 10⁷ M^-1. 323/A3 was produced by immunization with a human breast cancer cell line and has an affinity of 1.87 x 10⁹ M^-1.

Binding of both Abs to LS174T spheroids was similar at 4°C, but binding of 17-1A was 8–10-fold less than that of 323/A3 at 37°C. Despite this difference, the toxicity of ¹²⁵I-17-1A in spheroids after 7 days of incubation was similar to that of ¹²⁵I-323/A3. Autoradiography showed that 17-1A penetrated the spheroids much more deeply and evenly than did 323/A3. It appears that much of the radiation dose to spheroids treated with ¹²⁵I-323/A3 was wasted because of the uneven Ab distribution.

This study demonstrates the potential advantage of using Abs of lower affinity for ¹²⁵I radioimmunotherapy, because of their more even distribution. It also suggests that a large number of binding sites per cell may be a disadvantage if more ¹²⁵I is bound than is necessary to kill the cell, because this may slow Ab penetration.

¹ This research was supported in part by National Cancer Institute Grant R29 CA52285.

² To whom requests for reprints should be addressed, at SRI International, 333 Ravenswood Ave., Menlo Park, CA 94025.

Received 3/ 2/92. Accepted 6/23/92.

This article has been cited by other articles:

				C. P. Graff and K. D. Wittrup Theoretical Analysis of Antibody Targeting of Tumor Spheroids: Importance of Dosage for Penetration, and Affinity for Retention Cancer Res., March 15, 2003; 63(6): 1288 - 1296. [Abstract] [Full Text] [PDF]

				G. P. Adams, R. Schier, A. M. McCall, H. H. Simmons, E. M. Horak, R. K. Alpaugh, J. D. Marks, and L. M. Weiner High Affinity Restricts the Localization and Tumor Penetration of Single-Chain Fv Antibody Molecules Cancer Res., June 1, 2001; 61(12): 4750 - 4755. [Abstract] [Full Text] [PDF]