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Page 126 Bibi et al. J Transl Genet Genom 2024;8:119-161 https://dx.doi.org/10.20517/jtgg.2023.50

vaccine coding for PAP could augment PAP-specific T-cell activity after sipuleucel-T treatment [110,111] .
Despite an equal half increase in survival of four months, this is a competitor for drugs such as docetaxel,
abiraterone, radium 223, cabazitaxel, and enzalutamide, which are licensed for this stage of prostate
cancer [112-114] . A better outcome in the longer lifespan may have been achieved in subjects with less disease
pressure and proof of immune response to the PAP (prostatic acid phosphatase) antigen potent in relation
to anyone like antigen-specific IgG and T cells [115-117] . The study revealed a stronger Th2 response with DNA
immunization, suggesting potential benefits from administering DNA immunization before sipuleucel-
T [118-120] . Despite advancements, surgery remains crucial for PAP-positive prostate cancer patients,
indicating the importance of monitoring serum PAP levels in clinical practice [117,120] .

Prostate stem cell antigen
In research and studies conducted by researchers, HLA-A2-restricted PSCA peptides have been identified to
induce In vitro tumor-reactive CTL responses [121-123] . Elevated levels of CD8+ T cell lymphocytes recognize
these peptides which were found in the blood of prostate cancer subjects. Additionally, an HLA-A24-
presented peptide stimulating CTLs in PCa subjects was discovered . The TRAMP mouse model, which
[124]
mimics the production and display of PSCA during prostate cancer progression, was used to study the
immunotherapeutic potential of PSCA. Vaccination with a viral vector expressing PSCA, following priming
by PSCA cDNA, significantly increased survival rates in TRAMP mice in the presence of prostate
intraepithelial neoplasia compared to the control group .
[125]
Moreover, in another study utilizing this mouse model, recombinant DNA with modified vaccinia virus
Ankara vectors, which codes for PSCA, STEAP1, prevented PCa progression . Treatment with unbound
[126]
anti-PSCA antibody 1G8 reduced metastasis formation, increased long-term survival, and slowed xenograft
growth. Mechanistic studies revealed that target cross-linking was necessary for the Fc-independent
induction of cell destruction and death. PSCA is considered a target for immunotherapy using antibodies.
Mice with xenografts experienced cytotoxicity and remission after receiving anti-PSCA mAbs combined
with the toxin maytansinoid [127-129] .

Chimeric and human anti-PSCA antibody radio conjugates specifically target xenografts that are PSCA-
positive and display anticancer effects in vivo. Moreover, bispecific antibodies designed to target prostate
stem cell antigen and CD3 on human T cells activate immune-effector cells, leading to the elimination of
tumor cells [129-131] . Altered T cells expressing chimeric-antigen receptors targeting PSCA have demonstrated
high efficacy in lysing PSCA-expressing cells. In a recent study using an immunocompetent mice model of
prostate and pancreatic tumors expressing PSCA, the safety and effectiveness of PSCA-CAR T cells were
evaluated. Researchers observed both safety and long-lasting antitumor immune responses with PSCA-CAR
T cells, despite PSCA expression in various organs, such as stomach, prostate, and bladder. All preclinical
experiments highlight the potential of harnessing endogenous immunity against PSCA+ prostate cancers.
Ongoing clinical trials are evaluating PSCA-targeted CAR-T cell therapies, along with a study involving
CAR-T cells and BiTE antibodies [132-134] .

DNA mismatch repair deficiency, microsatellite instability, high tumor mutational burden
DNA mismatch repair deficiency (dMMR), microsatellite instability (MSI-H), and increased tumor load of
mutations are significant for cancer biology and therapy, because they influence the production and
identification of neoantigens, which are new peptides formed from mutant proteins presented to the
immune system by tumor cells. Neoantigens can trigger an antitumor immune response with stimulation of
T cells, a subset of immune cells capable of removing cancer cells. However, tumor cells sometimes employ
various strategies to evade or suppress the immune system. The detection of MSI-related prostate cancer