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[35]
system's ability to eliminate cancerous cells . Preclinical studies have shown promising results, with CAR T
cells effectively recognizing and killing prostate cancer cells in laboratory models. However, there are
significant challenges to the use of CAR T cell therapy in prostate cancer. One of the main concerns is the
potential for off-tumor toxicity, where CAR T cells attack not only cancer cells but also healthy tissues that
express low levels of PSMA or other targeted proteins . Additionally, prostate cancer cells can develop
[36]
resistance to CAR T cell therapy by downregulating the expression of PSMA, which allows them to evade
immune detection. This highlights the need for further research to improve the specificity and durability of
CAR T cell therapies for prostate cancer.

Dendritic cell vaccines
Dendritic cell vaccines are a promising cell-based therapeutic approach in the treatment of prostate cancer.
Dendritic cells are Toll-like receptors-a- a type of antigen-presenting cell that plays a critical role in
initiating immune responses. Dendritic cell vaccines are designed to activate the patient's immune system
by introducing tumor-associated antigens (TAAs) that help the immune system recognize and target
prostate cancer cells . The most well-known dendritic cellular immunotherapy in prostate cancer
[37]
treatment is sipuleucel-T (Provenge), the first cancer vaccine approved by the FDA for the treatment of
metastatic castration-resistant prostate cancer (CRPC). Sipuleucel-T is made by isolating a patient’s
dendritic cells, exposing them to a protein found in prostate cancer cells, and then re-infusing them into the
patient to stimulate an immune response . Clinical trials have demonstrated that sipuleucel-T can extend
[38]
overall survival in patients with metastatic prostate cancer, although its effects on tumor shrinkage and
progression-free survival have been limited. Despite their potential, dendritic cell vaccines face several
hurdles. The manufacturing process is labor-intensive and expensive, making it difficult to produce large
volumes of gene-edited products like cells, tissues, and organisms. Additionally, the immune responses
generated by these vaccines are often weak and require combining with other immunotherapies like
immune checkpoint inhibitors necessary to achieve more robust clinical outcomes .
[39]

Natural killer cells and adoptive cell transfer
Natural killer (NK) cells are another type of immune cell being explored for their potential use in prostate
cancer treatment. NK cells are part of the body’s innate immune system and can recognize and kill tumor
cells without prior sensitization . Research has focused on enhancing the cytotoxicity of NK cells against
[40]
prostate cancer cells by either populating them in the laboratory or genetically modifying them to enhance
their activity. For example, NK cells can be engineered to express CARs similar to those used in CAR T cell
therapy, allowing them to effectively target prostate cancer-specific antigens such as PSMA . However,
[41]
challenges remain in improving the persistence and trafficking of NK cells to the tumor site. CAR T cells,
dendritic cell vaccines, and NK cell therapies hold several promises, but several challenges must be
addressed before they can become widely adopted in clinical practice. One of the key issues is immune
evasion by prostate cancer cells, which can modify their surface proteins or create an immunosuppressive
microenvironment that limits the effectiveness of immune-based therapies . Furthermore, significant
[42]
immune-related adverse events, such as cytokine release syndrome (CRS), can lead to severe systemic
inflammation and even death . The cost of cell therapies is another major barrier to their widespread use.
[43]
For instance, treatments with CAR T cell therapy and dendritic cell vaccines require personalized
manufacturing processes, which drive up costs and limit accessibility. Efforts are ongoing to streamline
production and develop off-the-shelf cell therapies, but these approaches are still in their early stages of
development.

CLINICAL APPLICATIONS AND TRIALS IN PROSTATE CANCER TREATMENT
Gene and cell therapies for prostate cancer are at various stages of clinical trials, each designed to evaluate
the safety, efficacy, and feasibility of these cutting-edge approaches. Many of the trials in phase I or II stages