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Page 124 Bibi et al. J Transl Genet Genom 2024;8:119-161 https://dx.doi.org/10.20517/jtgg.2023.50

Figure 2. Schematic view of target proteins for immunotherapy, mostly expressed and over-expressed in prostate cancer. Prostate
cancer mostly expressed target proteins for immunotherapy such as prostate-specific antigen (PSA), PSMA (prostate-specific
membrane antigen), prostatic acid phosphatase, PSCA (Prostate stem cell antigen), dMMR (DNA mismatch repair deficiency), MSI-H
(microsatellite instability), TMB-H (high tumor mutational burden), prostein, TARP (T-cell receptor gamma alternate reading frame
protein), Transient receptor potential melastatin 8 (Trp-p8), six transmembrane epithelial antigen of prostate-1 (STEAP1), NY-ESO-1
and overexpressed proteins such as parathyroid hormone-related protein, human telomerase reverse transcriptase (hTERT), survivin,
HER-2/neu, EGFR, HER-4 (Epidermal Growth Factor Family), EphA2 (Erythropoietin producing hepatocellular receptor tyrosine kinase
class A2), SSX (Synovial sarcoma X-chromosome break point protein), EpCAM(epithelial cell adhesion molecule), RIPK2 (receptor-
interacting protein kinase 2).

Mostly expressed target proteins in prostate tissues
Prostate-specific antigen (PSA), a protein exclusive to prostate; prostate-specific membrane antigen
(PSMA), a membrane protein present in prostate; prostatic acid phosphatase (PAP), an enzyme associated
with prostate; prostate stem cell antigen (PSCA), an antigen linked to prostate stem cells; prostein, a
protein specific to prostate; TARP (T cell-receptor gamma alternate reading frame protein), a peptide
involved in T cell receptor signaling; Trp-p8, a protein relevant to prostate cancer; six-transmembrane
epithelial antigen of the prostate 1 (STEAP1), a transmembrane protein associated with prostate;
NY-ESO-1, a specific antigen with relevance to tumors [Figure 2].

Prostate-specific antigen
The presence of prostate-specific antigen (PSA) in a high proportion of prostate cancer (PCa) tissues makes
it a commonly applicable serum marker for identifying and monitoring PCa. PSA, a serin-protease similar
to kallikrein, is usually displayed in prostate epithelial cells [72-74] . Studies have identified PSA-derived
peptides that activate tumor-reactive CD8+ cytotoxic T lymphocytes (CTLs) when presented by human
leukocyte antigen-A2 (HLA-A2) and HLA-A3 [75-77] . Simultaneous induction of tumor-reactive CTLs and
HLA-A2/A3-restricted epitopes of PSA has been achieved using specific oligopeptides [78-80] . Additionally,
HLA-A24-restricted PSA peptides elicited peptide-specific CTLs in PCa patients and HLA-A*2402-
restricted CTLs in transgenic mice [81-83] . The role of various HLA class I and II molecules is to present
immunogenic PSA peptides [84,85] . Efforts to optimize active immunotherapy delivery methods have gained
attention, such as using adeno-associated virus-based vectors to transduce dendritic cells (DCs). These
[86]
modified DCs stimulated PSA-specific CTLs more efficiently than protein-pulsed DCs In vitro . In mouse