ANTIBODY TRANSPORT IN CULTURED TUMOR-CELL LAYERS

This review summarizes our recent in vitro studies of the factors affe cting the tumor penetration of immunoconjugates. The studies were desi gned to probe the mechanisms of diffusion and convection, using a cult ured layer of mouse melanoma cells as a model tumor cell layer and an antibody to the murine transferrin receptor as a model ligand. Transpo rt of the binding antibody was observed to be slower than that of a no n-binding control, a result that is consistent with the ''binding site barrier'' hypothesis (Fujimori et al., J. Nucl. Med., 31: 1191-1198, 1990). Internalization of the antibody/receptor complex was necessary for this effect to be observed, implying that intracellular traffickin g is a determinant of net tumor transport rates. Convective fluid flow exhibited a dependence on cell density that is consistent with a Pois euille flow model, suggesting that convective transport occurs as lami nar how in tortuous channels. Implications for immunoconjugate therapy , limitations of the approach, and future directions of the research p rogram are discussed. (C) 1998 Elsevier Science B.V.