Related Experiment Video
Updated: Sep 16, 2025
Microarray-based Identification of Individual HERV Loci Expression: Application to Biomarker Discovery in Prostate Cancer
Published on: November 2, 2013
Human Kallikrein 2: A Novel Lineage-Specific Surface Target in Prostate Cancer
Fei Shen1, Ryan Smith1, Theresa McDevitt1
1Johnson & Johnson, Spring House, Pennsylvania.
Purpose:
Targeted therapies for metastatic prostate cancer are limited, highlighting the need for novel drug targets and mechanisms of action (MoA). Human kallikrein 2 (KLK2) is a prostate-specific antigen expressed across the prostate cancer disease continuum. However, it was not recognized as a therapeutic target for prostate cancer in the past due to limited evidence of its cell surface expression. In this study, we systematically characterized KLK2 expression in prostate cancer, confirmed its cell surface expression, and demonstrated the preclinical efficacy of three KLK2-targeting therapeutics with distinct MoA.
Experimental Design:
The KLK2 expression profile in different stages of prostate cancer and its cell surface expression were confirmed by IHC and multiplex immunofluorescent staining. The preclinical efficacy of three KLK2-targeting therapeutics was characterized using in vitro prostate cancer cell lines, patient-derived material, and in vivo xenograft mouse models.
Results:
KLK2 was found to be robustly and homogeneously expressed in localized prostate cancer and metastatic hormone-sensitive prostate cancer, whereas some heterogeneity was observed in the visceral lesions of metastatic castration-resistant prostate cancer. KLK2 expression was more specific than that of other prostate cancer target antigens. Although KLK2 is traditionally described as a secreted protease, our results demonstrated its cell surface expression in both prostate cancer cell lines and patient-derived tumors. Notably, targeting KLK2 with three different MoAs, including bispecific T-cell redirector, targeted α-radioligand, and autologous chimeric antigen receptor T cells, showed potent in vitro activity and robust in vivo tumor control.
Conclusions:
Our study establishes KLK2 as a highly prostate-specific cell surface target. Targeting KLK2 with various MoAs represents novel therapeutic approaches for advanced prostate cancer. See related commentary by Blinka and Yu, p. 4393.
Insights
Human kallikrein 2 (KLK2) is a prostate-specific antigen now confirmed as a cell surface target for prostate cancer (PCa). Targeting KLK2 with novel therapeutics shows significant preclinical efficacy in advanced PCa.
Area of Science:
- Oncology
- Molecular Biology
- Drug Discovery
Background:
- Metastatic prostate cancer (PCa) lacks effective targeted therapies, necessitating new drug targets and mechanisms of action (MoA).
- Human kallikrein 2 (KLK2), a prostate-specific antigen, has been underexplored as a therapeutic target due to prior assumptions about its expression.
- Limited evidence of cell surface expression historically hindered KLK2's recognition as a viable target in PCa.
Purpose of the Study:
- To systematically characterize KLK2 expression across the PCa disease continuum.
- To confirm the cell surface expression of KLK2 in prostate cancer.
- To evaluate the preclinical efficacy of KLK2-targeting therapeutics with distinct MoA.
Main Methods:
- Immunohistochemistry and multiplex immunofluorescent stainings to assess KLK2 expression profiles.
- In vitro studies using PCa cell lines and patient-derived material.
- In vivo xenograft mouse models to evaluate therapeutic efficacy.
Main Results:
- KLK2 demonstrated robust and homogeneous expression in localized and hormone-sensitive PCa, with some heterogeneity in metastatic castration-resistant PCa.
- KLK2 exhibits higher specificity compared to other PCa target antigens and is confirmed to be expressed on the cell surface.
- Three distinct KLK2-targeting therapeutics (bispecific T-cell redirector, targeted alpha-radioligand, CAR T) showed potent in vitro activity and significant in vivo tumor control.
Conclusions:
- KLK2 is validated as a highly prostate-specific cell surface target for PCa.
- Targeting KLK2 presents promising novel therapeutic strategies for advanced prostate cancer.
- The diverse MoA evaluated offer multiple avenues for developing effective KLK2-based therapies.
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
01:27Transducer Mechanism: Enzyme-Linked Receptors
Major types that are helpful drug targets include: