The secreted tumor-associated antigen 90K is a potent immune stimulator

抗原 免疫系统 生物 单克隆抗体 免疫学 抗体 肿瘤抗原 分子生物学 免疫疗法
作者
A. Ullrich,I Sures,M. D'Egidio,Bahija Jallal,Timothy J. Powell,Ronald Herbst,A. Dreps,Md Suhil Ibne Azam,Mark P. Rubinstein,Clara Natoli
出处
期刊:Journal of Biological Chemistry [Elsevier BV]
卷期号:269 (28): 18401-18407 被引量:192
标识
DOI:10.1016/s0021-9258(17)32322-0
摘要

Immunization of mice with conditioned media from human breast cancer cells yielded the monoclonal antibody SP-2, which recognized an antigen of approximately 9&95 kDa.This protein, designated 90K, was found to be present in the serum of healthy individuals and at elevated levels in the serum of subpopulations of patients with various types of cancer and AIDS.Here we report the primary structure of the SP-2 antigen and demonstrate its relationship to a family of proteins which carry a scavenger receptor cysteine-rich domain.Northern blot analysis of normal tissues, primary tumors, and tumor-derived cell lines indicates a broad expression spectrum of the 9OK gene at widely varying levels.Functional characterization reveals stimulatory effects of 90K on host defense systems, such as natural killer cell and lymphokine-activated killer cell activity, and indicates that its immunostimulatory effects may be mediated through the induction of interleukin-2 and possibly other cytokines.Monoclonal antibodies (mAbs)' recognizing tumor-associated antigens (TAAs) for a number of cancer types have been reported, but the proportion of those that recognize molecules released in significant amounts into the bloodstream is small (for review, see Ref. 7).Moreover, the biological functions and possible roles of such TAAs in the context of tumor-host relationships are largely unknown.Previous studies using mAb SP-2, derived from the fusion of spleen cells of mice repeatedly immunized with conditioned medium of human breast cancer cell cultures, led to the identification of the 90K glycoprotein, which was found in both healthy individuals and at elevated

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