Search

The treatment for cancer has undergone a paradigm shift in recent years due to the introduction of cellular-based targeted therapies and immunotherapy, particularly Chimeric Antigen Receptor (CAR)-T Cell Therapy. This narrative review examines the biology of how CARs function, along with the advances made in the development of CAR construct design over the last 3 decades. These advances include the addition of co-stimulatory signals such as CD28 and 4-1BB in the new generation CARs that improved T Cell proliferation and longevity. There have been multiple different Cancer types that have demonstrated a high degree of effectiveness using CAR-T Cell therapy, and the US FDA has approved the use of CAR-T Cell therapies for treatment of certain hematological malignancies, specifically B Cell Acute Lymphoblastic Leukemia and Diffuse Large B Cell Lymphoma. However, there remains a significant limitation for the use of CAR-T Cell therapies for solid tumor therapies. Three major limitations preventing CAR-T Cell therapies from being used as an effective treatment for solid tumors include the existence of an immune suppressive tumor microenvironment (TME), the physical barriers preventing T Cells from migrating to tumor sites, as well as tumor antigen heterogeneity preventing treatment efficacy. This review discusses potential emerging modalities for overcoming some of these limitations, including the development of "armored" CAR-T Cells, the use of multi-antigen targeting strategies to prevent antigen escape, and the development of combinatorial approaches to modulate the TME. Lastly, this review discusses future opportunities in the development of CAR-T Cell therapies, including the development of "off-the-shelf" allogeneic CAR-T Cells, in vivo gene delivery systems to create CAR-T Cells, and gene editing via CRISPR/Cas9 systems to increase the safety profile of CAR-T Cells and expand their therapeutic application beyond blood cancers.

The growing global population has amplified the demand for food, making the international trade of livestock a significant threat to animal and public health due to the increased risk of zoonotic disease transmission through animal movement or the consumption of their products. Biosecurity measures (BSMs) and vaccination are two essential tools that, when effectively implemented, can significantly reduce the spread of diseases from livestock. However, their failure not only escalates the burden of disease but also compromises food security and public health. Weak or poorly enforced BSMs can undermine the efficacy of vaccinations, creating challenges against disease prevention efforts. Conversely, robust BSMs such as nutritional and environmental management, routine monitoring of disease, farm management, and hygiene provide a critical foundation for successful vaccination programs by minimizing disease exposure and ensuring vaccine effectiveness. Inappropriate vaccination administration, inadequate cold chain management, and the frequency of immunosuppressive illnesses are also reported as contributing factors to vaccine failure. This review delves into the interconnected roles of BSMs and vaccination, unveiling the importance of the implementation of biosecurity principles in preventing vaccine failure. It also explores how the integration of biosecurity practices and vaccination strengthens animal health systems, mitigates zoonotic risks, and enhances overall food safety. Future research should concentrate on integrated biosecurity techniques by strengthening on-farm biosecurity protocols, proper handling and administration of vaccines, careful disease surveillance, and awareness programs thereby increasing the resilience of our livestock industry against notable diseases.