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TGM4: an immunogenic prostate-restricted antigen.

Zoila A Lopez-Bujanda^1,2,3,4, Aleksandar Obradovic², Thomas R Nirschl^1,3

¹Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Journal for Immunotherapy of Cancer

|July 1, 2021

Summary

This summary is machine-generated.

Researchers identified transglutaminase 4 (TGM4) as a novel, immunogenic prostate-specific antigen. TGM4 shows promise as a new immunotherapy target for prostate cancer, particularly metastatic castration-resistant prostate cancer (CRPC).

Keywords:

antigens immunogenicity prostatic neoplasms vaccine

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Area of Science:

Oncology
Immunology
Molecular Biology

Background:

Prostate cancer (PCa) is a leading cause of cancer death in men, with progression to metastatic castration-resistant prostate cancer (CRPC) being fatal.
Current immunotherapies like sipuleucel-T offer limited survival benefits, highlighting the need for novel immunogenic tumor-associated antigens (TAAs).

Purpose of the Study:

To identify and characterize novel prostate-restricted TAAs for PCa immunotherapy.
To evaluate the immunogenicity and potential of TGM4 as a therapeutic target for CRPC.

Main Methods:

Differential gene expression analysis of castration-resistant prostate epithelial cells.
Evaluation of androgen-responsive genes in murine and human tissues.
Immunostaining and analysis of TGM4 expression in human cancers (The Cancer Genome Atlas).
In vitro and in vivo immunogenicity assays using dendritic cells and T cells from healthy donors and patients with PCa.

Main Results:

Transglutaminase 4 (TGM4) was identified as a highly expressed, prostate-restricted TAA.
Elevated TGM4 expression correlated with unfavorable prognosis in PCa patients.
TGM4 demonstrated potent immunogenicity, expanding CD8 and CD4 T cells more effectively than PAP or PSA.
TGM4 vaccination elicited a significant IgG antibody response in PCa patients.

Conclusions:

TGM4 is a promising immunogenic, prostate-restricted antigen.
TGM4 has potential for development as a novel immunotherapy target for prostate cancer.
Further research into TGM4-based immunotherapies is warranted for CRPC treatment.