当前位置： SCI文献检索 > CANCER RESEARCH期刊下所有文献 > Rapid tumor penetration of a single-chain Fv and comparison with other immunoglobulin forms.

Rapid tumor penetration of a single-chain Fv and comparison with other immunoglobulin forms.

Abstract：

:Single-chain antigen-binding proteins, or sFvs, represent potentially unique molecules for targeted delivery of drugs, toxins, or radionuclides to a tumor site. In previous studies (Cancer Res., 51:6363-6371, 1991) using a human colon carcinoma xenograft model, it was demonstrated that the sFv has an extremely rapid plasma and whole body clearance, as compared to intact IgG or Ig fragments. One potential consequence of the rapid sFv pharmacokinetic properties was the reduced percentage of injected dose/g of the radiolabeled sFv found in the tumor throughout a range of time points. The present study was designed to define the tumor penetration properties of a radiolabeled sFv in comparison with other Ig forms. 125I-labeled sFv, Fab', F(ab')2, and IgG forms of monoclonal antibody CC49, directed against the human pancarcinoma antigen TAG-72, were used to target the LS-174T human colon carcinoma xenograft in athymic mice. At various time points after systemic Ig administration, quantitative autoradiographic analyses of surgically removed tumors were used to define the rate and degree of penetration of the various Ig forms. These studies revealed that most of the intact IgG delivered to the tumor was concentrated in the region of or immediately adjacent to vessels, while the sFv was more evenly distributed throughout the tumor mass. The distributions of the Fab' and F(ab')2 fragments showed intermediate penetration in a size-related manner. The sFv demonstrated maximum tumor penetration at 0.5 h postinjection, while the intact IgG reached an equivalent degree of penetration at 48 to 96 h postinjection. These studies thus reveal a greater degree of uptake throughout the tumor for the sFv than would be expected by gross analyses of percentage injected dose/g and demonstrate an extremely rapid tumor penetration of the sFv. These studies should aid in the rational design of potential applications of drug-, toxin-, and radionuclide-conjugated sFvs in cancer therapy.

journal_name

Cancer Res

journal_title

Cancer research

authors

Yokota T,Milenic DE,Whitlow M,Schlom J

subject

Has Abstract

pub_date

1992-06-15 00:00:00

pages

3402-8

issue

eissn

0008-5472

issn

1538-7445

journal_volume

pub_type

杂志文章

在线工具

Rapid tumor penetration of a single-chain Fv and comparison with other immunoglobulin forms.