Homeobox protein NKX-3.1 (NKX3.1) (NKX3.1)

Homeobox protein NKX-3.1 is a prostate-specific transcription factor that plays a critical role in the development and maintenance of the prostate gland (UniProt: P78337). It functions as a tumor suppressor, and its expression is often reduced or lost during the progression of prostate cancer; however, it remains a viable target for immunotherapy due to its highly restricted expression pattern in prostatic tissue. NKX3.1-specific T cells, particularly TCR-engineered T cells like KITE-718, are designed to recognize NKX3.1 peptides presented by HLA-A*02:01 (NCT04055493). These therapeutic T cells aim to selectively eliminate prostate cancer cells while sparing non-prostatic tissues. Clinical development focuses on metastatic castration-resistant prostate cancer (mCRPC), where NKX3.1 serves as a lineage-specific antigen. The therapy involves the infusion of autologous T cells that have been genetically modified to express a TCR specific for the NKX3.1/HLA complex, allowing for the targeting of an intracellular protein that is otherwise inaccessible to conventional antibody-based therapies.

Other names

NKX3-1NKX3ABAPX2Homeobox protein NK-3 homolog A

T-cell receptor (TCR) engineered T cells recognize specific NKX3.1-derived peptides presented by Human Leukocyte Antigen (HLA) molecules on the surface of cancer cells, leading to targeted cell lysis (PMID: 31462510).