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Bibi et al. J Transl Genet Genom 2024;8:119-161 https://dx.doi.org/10.20517/jtgg.2023.50 Page 125

models, PSA has successfully triggered specific T cell responses. Researchers have explored binding
vaccination techniques by androgen deprivation, showing enhanced CTL responses in HLA-A*0201/human
PSA-twice transgenic mice when castrated before immunization by a PSA-presenting vaccinia virus.
Androgen ablation was found to reduce CD4+T cell tolerance to prostate-specific antigens, suggesting that
targeted immunotherapy for PCa might be more effective post androgen ablation [87,88] .

Typically, patients with increased PSA levels are transferred to a urologist for identifying and clarifying
testing, which could be a prostate MRI or a biopsy . Among the ten studies that were included, a variety of
[89]
estimates for PSA's accuracy were discovered. However, the methodologies of the included studies were
only vaguely described in that review, and it was significantly unclear whether any of them assessed PSA in
patients who were symptomatic or asymptomatic or whether any of them were applied to primary care
populations. In a review of the literature, researchers noted the dearth of studies addressing the first level of
care and the majority of prostate-specific antigen tests are conducted [90]

Prostate-specific membrane antigen
Prostate-specific membrane antigen (PSMA) was initially discovered in various natural active tissues such
as the brain, salivary gland, breast epithelium, renal tubular epithelium, and small intestine. While it was
highly tissue-specific, non-prostatic tissues had significantly lower expression levels, ranging from 100 to
1,000 times lower. In prostate cancers, especially in advanced undifferentiated metastatic hormone-
refractory prostate cancer (HRPC), PSMA serves as a marker/identifier for healthy prostate cells and is
commonly present in major prostate tumors. Studies, both in vivo and In vitro, have explored the optimal
antigen to trigger T cell responses, demonstrating that co-transducing genes encoding the extracellular
portion of PSMA, a costimulatory peptide, with an adenoviral vector, efficiently triggers targeted T cell
responses and fosters immune reactions against tumors in murine models [91-95] . PSMA has also emerged as a
promising target for antibody treatment due to its surface expression on prostate cancer cells. Various anti-
PSMA monoclonal antibodies, such as J591, linked to ricin A, bismuth-conjugated mab J591, have exhibited
target-specific cytotoxicity against PSMA-expressing prostate cancer cells. Additionally,
radioimmunotherapy employing antibody-conjugates of J415 and J591, bound to radioactive isotopes, has
demonstrated preferential accumulation in live tumor regions in xenograft models, leading to potent and
targeted anticancer effects both in vitro and in vivo [96-101] . Furthermore, PSMA has become a recognized
target for prostate cancer treatment, with recent FDA approval of 177Lu-PSMA-617 for the treatment of
advanced metastatic castrate-resistant prostate cancer (mCRPC) following successful outcomes in phase III
VISION trials. There are ongoing developments in PSMA-targeted radiopharmaceuticals, including
substances like J591 and TLX591 that utilize monoclonal antibodies to target PSMA. Additionally, small
compounds such as PSMA 617, PSMA T&I, and MIP 1095 are being employed to target PSMA in these
contexts .
[102]

Prostatic acid phosphatase
The principal protein released by prostate epithelial cells is PAP (Prostatic acid phosphatase), primarily
found in benign and cancerous prostate tissue. Related identifications indicate low PAP mRNA display in
non-prostate specific tissues such as kidney, testis, and placenta . Immunogenic PAP-derived peptides
[66]
binding with HLA-A2 were discovered, leading to specific tumor rejection in vivo [103-106] . Vaccination
techniques using PAP target antigen showed immunotherapeutic potential, activating PAP-CD8+ cytotoxic
T-lymphocytes and inhibiting tumor growth in animal models [107-110] . Sipuleucel-T, a binding together
protein of GM-CSF and PAP, demonstrated effectiveness in phase III trials for advanced prostate cancer
patients. Patients receiving sipuleucel-T had a 22% lower risk of dying and a median survival of 25.8 months
compared with 21.7 months in placebo group. Researchers explored whether subsequent doses of a DNA