Abstract
This study identifies and characterizes the antigen recognized by monoclonal antibody (mAb) 14C5. We compared the expression of antigen 14C5 with the expression of eight integrin subunits (alpha1, alpha2, alpha3, alphav, beta1, beta2, beta3, and beta4) and three integrin heterodimers (alphavbeta3, alphavbeta5, and alpha5beta1) by flow cytometry. Antigen 14C5 showed a similar expression to alphavbeta5 in eight different epithelial cancer cell lines (A549, A2058, C32, Capan-2, Colo16, HT-1080, HT-29, and SKBR-3). Specific binding of P1F6, an anti-alphavbeta5 specific antibody, was blocked by mAb 14C5. After transient expression of alphavbeta5 in 14C5-negative Colo16 cells, mAb 14C5 was able to bind a subpopulation of alphavbeta5-positive cells. We evaluated the tissue distribution of the 14C5 antigen in colon (n = 20) and lung (n = 16) cancer tissues. The colon carcinoma cells stained positive for 14C5 in 50% of tumors analyzed, whereas bronchoalveolar lung carcinoma and typical carcinoid were not positive for the antigen. More common types of non-small cell lung cancer, i.e., squamous (n = 5) and adenocarcinoma (n = 3), stained positive in 2 of 5 squamous carcinomas and in 1 of 3 investigated adenocarcinoma. Colon (95%) and lung (50%) carcinoma tissues showed extensive expression of antigen 14C5 in the stroma surrounding the tumor cells and on the membrane of the adjacent fibroblasts. We show for the first time that mAb 14C5 binds the vascular integrin alphavbeta5, suggesting that mAb 14C5 can be used as a screening agent to select colon and lung cancer patients that are eligible for anti-alphavbeta5-based therapies.
Highlights
In search of new antibody therapeutics for therapy of metastatic breast cancer, several mouse monoclonal antibodies were developed against epitopes on the extracellular membrane of SK-BR-3 human breast cancer cells [1]. One of these mAbs is the IgG1 mAb 14C5, which recognizes an extracellular plasma membrane antigen expressed on SK-BR-3 and MCF-7 human breast cancer cells [1, 2]
antigen 14C5 (Ag 14C5) is located on the cell membrane of the carcinoma cells
We have previously shown the biodistribution and stable antigen-binding properties of radio-iodinated mAb 14C5 [5, 6] and its Fab and F(ab¶)2 fragments [7]. mAb 14C5 readily internalizes in cancer cells, which makes it an attractive candidate for radioimmunotherapy [6]
Summary
In search of new antibody therapeutics for therapy of metastatic breast cancer, several mouse monoclonal antibodies (mAb) were developed against epitopes on the extracellular membrane of SK-BR-3 human breast cancer cells [1]. One of these mAbs is the IgG1 mAb 14C5, which recognizes an extracellular plasma membrane antigen expressed on SK-BR-3 and MCF-7 human breast cancer cells [1, 2]. In normal tissues and stroma surrounding in situ carcinomas of the breast (n = 15), no expression of the Ag 14C5 occurred [2]. Low-level staining of myoepithelial cells was sometimes observed in biopsies of breast tissue and in tubular cells of the kidney
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