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primarily in wealthier countries, despite trials/seeking of legislative approval ongoing in developing
countries. This raises concerns about health equity as patients in low- and middle-income countries may
[56]
not have access to these potentially life-saving treatments .

Regulatory hurdles
Gene and cell therapies face complex regulatory hurdles before they are approved for widespread use.
Regulatory agencies such as the FDA and EMA require extensive safety and efficacy data sets, which can
take years to collect in clinical trials. This long approval process delays the availability of new therapies and
[57]
increases development costs . There are also challenges in developing appropriate quality control measures
for manufacturing gene and cell therapies. This is due to their complex and personalized nature. In response
to these challenges, some regulatory agencies have introduced accelerated approval pathways for gene and
cell therapies that show promising early results. However, these pathways still require rigorous post-market
surveillance to ensure that these therapies are safe and effective in the long term. Therefore, there is a need
for phase 4 clinical studies for all licensed gene editing and cell therapy modalities in the post-market
setting.

FUTURE DIRECTIONS AND PROSPECTS FOR GENE AND CELL THERAPY IN PROSTATE
CANCER
Emerging technologies
The future of gene and cell therapy in prostate cancer treatment will be shaped by several emerging
technologies that promise to address current limitations and enhance therapeutic efficacy. Next-generation
CAR T cell technology is focused on improving the specificity and safety of these therapies. One major
approach is dual-targeted CAR T cells engineered to recognize multiple antigens in prostate cancer cells.
This can potentially overcome antigen escape and enhance treatment response. CAR T cells targeting both
PSMA and prostate stem cell antigen (PSCA) have shown promise in preclinical models by targeting a
broader range of tumor cells and reducing the risk of antigen loss . Moreover, ARM-CAR T cells are being
[58]
explored to improve the persistence and functionality of CAR T cells within the hostile tumor
microenvironment. These cells are designed with enhanced signaling domains that can sustain T cell
activation and survival, potentially leading to more responses in patients .
[59]

Innovations in gene delivery systems are addressing the challenges associated with targeting and
transformation efficiency. Nanoparticle-based delivery systems are being developed to deliver therapeutic
genes with precision and reduced immunogenicity. Lipid nanoparticles and polymer-based carriers are non-
viral vectors optimized for more effective gene transfer and reduced off-target effects. These systems can
also be engineered to release their payloads in response to specific stimuli present in the tumor
microenvironment, enhancing targeted delivery . Epigenetic modulations are gaining traction as they can
[60]
modify the expression of genes involved in tumor progression without altering the underlying DNA
sequence. Small molecules and epigenetic editing tools are being investigated to reverse aberrant gene
silencing or activation that contributes to prostate cancer development. For instance, drugs targeting DNA
methylation and histone modification are showing potential in reactivating tumor suppressor genes and
enhancing the efficacy of existing treatments .
[61]
Furthermore, combining gene and cell therapies with other modalities like oncolytic viruses continues to be
a key area that selectively infects and kills cancer cells. This combined gene therapy enhances the oncolytic
effect and promotes systemic antitumor immunity. For example, oncolytic viruses expressing therapeutic
genes that stimulate immune responses or sensitize tumors to other treatments are showing promise in
[62]
preclinical studies . Integrating gene and cell therapies with immunotherapies such as immune checkpoint