The selection of antibodies for targeted therapy of small-cell lung cancer (SCLC) using a human tumour spheroid model to compare the uptake of cluster 1 and cluster w4 antibodies

Abstract

Summary Spheroids of a small-cell lung cancer (SCLC) cell line POC were used to evaluate the uptake and penetration of two antibodies recognising different SCLC antigens. Spheroids approximately 300-400 gm in diameter were incubated with 1 jig ml-"25I-labelled NY.3DI 1, an antibody which reacts with the cluster I group antigen (neural cell adhesion molecule; NCAM) and ['25I]SWAI 1, which binds to the cluster w4 antigen. The rate of uptake of both antibodies was similar; an initially rapid phase was seen during the first 8 h and maximum uptake occurred by 24 h. This increased to about 100 txm after 4 h incubation with I or 100 fig ml-' SWAI 1. The results with I lg mlh' NY.3D1 were similar, but in the presence of 100 jg ml-' NY.3DI I penetration into the spheroid was deep and diffuse. These results demonstrate a major concentration-dependent difference in the uptake and penetration of cluster I and cluster w4 antibodies in this spheroid model and they have implications for the selection of antibodies for targeted therapy of SCLC.

Analysis of gene expression profiles in normal and neoplastic ovarian tissue samples identifies candidate molecular markers of epithelial ovarian cancer

“…2). The most highly ranked gene, CD24, was first proposed as a therapeutic target for lung cancer (17,18), and more recently as a diagnostic marker for breast cancer (19). This gene has been reported to have a role in increasing the motility of breast cancer cells (20).…”

Penetration and Binding of Monoclonal Antibody in Human Osteosarcoma Multicell Spheroids: Comparison of confocal laser scanning microscopy and autoradiography

“…Before slicing, the spheroids were washed twice in PBS, embedded in a few drops of TissueTek O.C.T. compound embedding medium (Miles), frozen in liquid nitrogen and cut into 20 p m thick sections (17). The sections were mounted on slides and analysed by CLSM.…”

Antibody constructs in cancer therapy

“…Using parameters derived from the literature their simulations were in qualitative and quantitative agreement with a variety of experimental datasets including kinetics and dose dependence of Ab uptake into spheroids [37][38][39][40][41][42] and biodistribution of Abs and Ab fragments into tumor xenografts as a function of affinity, molecular weight, and elimination half-life. 4,[43][44][45] During an initial loading phase, intratumoral diffusion competes with systemic clearance, and bound Ab moves toward the tumor core, whereas the concentration of free Ab at the tumor surface remains high.…”