Anti-KLK11 monoclonal antibody

Background: Kallikrein 11 (KLK11) is a newly discovered human kallikrein gene that is mainly expressed in the central nervous system and endocrine tissues. KLK11 has two alternative splicing isoforms, known as the brain type and prostate type. Many members of the human kallikrein gene family are differentially expressed in cancer and a few have potential as diagnostic/prognostic markers. Methods: In the present study, the expression of prostate type variant of KLK11 gene was analyzed by RT-PCR in 66 prostate cancer tissues. Tumors were pulverized, total RNA was extracted, and cDNA was prepared by reverse transcription. KLK11 was amplified by PCR using gene specific primers and its identity was verified by sequencing. Prostate tissues were then classified as KLK5 positive or negative based on eithidium bromide staining in agarose gels and image analysis. Results: KLK11 was found to be highly expressed in 43/66 (65%) of prostate cancer samples. We found a significant negative relationship between KLK11 expression and Gleason score (p = 0.004) and disease stage (p = 0.038). Serum total PSA concentration was found to be lower in patients with overexpression of KLK11 (p = 0.044). Conclusions: We conclude that down-regulation of the KLK11 gene in advanced and more aggressive tumors may open the possibility of being used as a future biological marker distinguishing the tumor aggressiveness as well as a useful prognostic biomarker for prostate cancer. (c) 2005 Elsevier B.V. All rights reserved.

Purpose: Human tissue kallikreins are a family of 15 secreted serine proteases. We have previously shown that the expression of several tissue kallikreins is significantly altered at the transcriptional level in lung cancer. Here, we examined the clinical value of 11 members of the tissue kallikrein family as potential biomarkers for lung cancer diagnosis. Experimental Design: Serum specimens from 51 patients with non-small cell lung cancer (NSCLC) and from 50 healthy volunteers were collected. Samples were analyzed for11 kallikreins (KLK1, KLK4-8, and KLK10-14) by specific ELISA. Data were statistically compared and receiver operating characteristic curves were constructed for each kallikrein and for various combinations. Results: Compared with sera from normal subjects, sera of patients with NSCLC had lower levels of KLK5, KLK7, KLK8, KLK10, and KLK12, and higher levels of KLK11, KLK13, and KLK14. Expression of KLK11 and KLK12 was positively correlated with stage. With the exception of KLK5, expression of kallikreins was independent of smoking status and gender. KLK11, KLK12, KLK13, and KLK14 were associated with higher risk of NSCLC as determined by univariate analysis and confirmed by multivariate analysis. The receiver operating characteristic curve of KLK4, KLK8, KLK10, KLK11, KLK12, KLK13, and KLK14 combined exhibited an area under the curve of 0.90 (95% confidence interval, 0.87-0.97). Conclusions: We propose a multiparametric panel of kallikrein markers for lung cancer diagnosis with relatively good accuracy. This model requires validation with a larger series and may be further improved by addition of other biomarkers.