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Page 128 Bibi et al. J Transl Genet Genom 2024;8:119-161 https://dx.doi.org/10.20517/jtgg.2023.50

[158]
prostate . TRPM8 is expressed more in stromal cells compared to normal epithelial prostate cells,
particularly androgen-sensitive cells. Although the activity of TRPM8 in prostate cancer is not clear, some
studies imply that it may have functional activity in cell survival, invasion, and metastasis [158-160] .
Consequently, it is a therapeutic target for the cure of prostate cancer and a possible marker for disease
identification [157-160] . A seven-span transmembrane protein, exhibiting a significant resemblance to Ca 2+
channel proteins, is encoded by the TRPM8 gene. Most prostate cancers exhibit the expression of TRPM8,
primarily limited in the prostate . Upon investigating differences from equivalent normal prostate tissue,
[156]
upregulation of it was observed in early-stage cancers. We discovered an HLA-A*0201-binding protein that
might incite tumor-reactive CTLs in vitro [111,161] .

Six transmembrane epithelial antigen of prostate-1
Iron and copper metabolism, as well as other cellular functions, are affected by the protein known as Six
[162]
transmembrane epithelial antigen of prostate-1 (STEAP1) . The protein is typically overexpressed in
prostate cancer cells, particularly those susceptible to androgens, the male sex hormones [163,164] . While
STEAP1 is usually expressed at low levels in several organs, it plays a significant role in influencing
epithelial-mesenchymal transition (EMT), leading to changes in the activities of cancer cells, making them
more mobile and aggressive. Consequently, STEAP1 may contribute to the growth, invasion, and metastatic
spread of prostate cancer [162,163] . Thus, it is plausible that STEAP1 could serve as both a biological marker and
a therapeutic target for prostate cancer [162,163] . Moreover, researchers have discovered three promiscuous
epitopes of CD4+ T cells and a various naturally occurring HLA-A2 restricted protein that can induce
cytotoxic T-lymphocytes in vivo and in vitro [106,165-169] . Some immunization techniques, utilizing viral or
recombinant cDNA vectors that code for mouse six-transmembrane epithelial antigen of prostate-1, have
shown increased efficacy in inducing particular T cell expression, slowing tumor development, and
lengthening longevity in mice models [126,170,171] .

Recent research indicates that STEAP1 may also be a promising target for immunotherapy using antibodies;
a pair of STEAP-specific monoclonal antibodies (mAbs) dramatically slowed the progression of PCa
[172]
xenografts (mice) .
NY-ESO-1
Nine out of twenty-three (39%) prostate cancer patients had NY-ESO-1 mRNA expression. In 12 of 23
(52%) PCa patient sera and in 5 of 9 (55%) tumors expressing NY-ESO-1, antibodies against the protein
were identified. However, neither mRNA copies nor NY-ESO-1 were identified in any of the studied BPH
patients . NY-ESO-1, a cancer testis antigen (CTA), is a peptide typically solely observed in the testis but
[173]
can occasionally be found in other malignancies, such as prostate cancer. NY-ESO-1 is a significant
immunogenic cancer testis antigen, which means that it can stimulate the body's production of antibodies
and T cells . Therefore, NY-ESO-1 might be a helpful immunotherapeutic target in cancer treatment that
[174]
[174]
leverages the immune system . Research revealed that 20 of 53 (38%) prostate cancer specimens had
NY-ESO-1 mRNA expression, with a higher prevalence observed in more advanced disease stages. While
none of the 78 subjects with localized prostate cancer had NY-ESO-1 antibodies, 10 of the 140 (7.1%)
patients with metastatic prostate cancer did. Some patients who had antibodies against NY-ESO-1 also
showed CD8 T cell responsiveness specific to NY-ESO-1. These results imply that prostate cancer
progression and aggressiveness are related to NY-ESO-1 expression and immunogenicity .
[175]

For subjects with prostate cancer, numerous clinical trials have been conducted or are currently underway
to evaluate the safety and efficacy of immunotherapy centered around NY-ESO-1. These trials encompass
various approaches, including immunization with recombinant NY-ESO-1 peptide in combination with the