Chimeric antigen receptor (CAR) T cell therapy has shown remarkable efficacy in hematologic malignancies, yet its translation to solid tumors remains a fundamental challenge. Immunologically “cold” tumors, characterized by poor T cell infiltration, dense stromal barriers, and a profoundly immunosuppressive tumor microenvironment (TME), continue to resist conventional CAR-T cell approaches. Armored CAR-T cells engineered to secrete interleukin-18 (IL-18) represent a promising fourth-generation strategy designed to overcome these limitations. IL-18 operates at the interface of innate and adaptive immunity, driving M1 macrophage polarization, dendritic cell maturation, NK cell activation, and the induction of CXCL9/CXCL10 chemokine gradients that restore lymphocyte trafficking into tumor tissue. To guide the rational design of these constructs, bioinformatics pipelines play an increasingly central role. Multi-omics integration of transcriptomic, proteomic, and single-cell RNA sequencing data enables precise tumor antigen selection, epitope prediction, and structural optimization of CAR constructs using tools such as AlphaFold, RosettaDock, and NetMHCpan. In silico safety screening further evaluates off-target toxicity risks and cross-reactivity against healthy tissues. Controlled IL-18 delivery strategies, including NFAT-inducible promoters, SynNotch logic-gated systems, and Granzyme B-cleavable pro-IL-18 constructs, provide spatial and temporal safeguards against systemic hyperinflammation. Preclinical evidence from xenograft and syngeneic models demonstrates enhanced tumor control, sustained T cell persistence, and induction of endogenous anti-tumor immunity. This review synthesizes current evidence and highlights how bioinformatics-guided engineering of IL-18 armored CAR-T cells offers a translatable framework for converting cold tumors into immunologically responsive, therapeutically tractable targets.

The H5N1 influenza threat is a significant issue to the overall health of the population in the world, and it demands new approaches in vaccine development and implementation. The critical path forward is the development of universal vaccine platforms, which provide long-term cross-protection against various H5N1 strains. This type of vaccines, based on conserved regions of viruses, is necessary to provide long term immunity against antigenic variation. The future of vaccines should be based on the ability to generate both cellular and humoral immunity and provide the greatest level of protection against a variety of viral variants. It is also crucial that agile manufacturing capacities are established, which can swiftly expand the production of vaccines to satisfy the demand in the world in the case of an influenza outbreak. The technology of mRNA vaccines, viral vectors, or microneedle patches can be adapted to novel strains rapidly and responds effectively to the situation when rapid and effective responses are required. Also, fair global distribution policies can be crucial to make it possible to make vaccines available to the population of low- and middle-income countries. The international response needs to focus on equity, whereby inequality in access to vaccines is minimized. This has been the ultimate solution of combining universal vaccines, cross-protection, agile production, and equity over the world to reduce the threat of H5N1 pandemic. By developing these measures, the world community can be more ready to the upcoming outbreak of influenza, and access to a vaccine can be timely, extensive, and efficient.

Antibiotic resistance among Gram-negative bacteria, particularly those capable of forming biofilms, has become a serious clinical challenge with limited treatment options. In this study, magnesium oxide nanoparticles (MgO NPs) were synthesized using a green, cost-effective approach based on aqueous leaf extract of Cymbopogon citratus (lemongrass) and evaluated for their antibacterial and antibiofilm potential against multidrug resistant (MDR) clinical isolates of Acinetobacter baumannii , Klebsiella pneumoniae , Pseudomonas aeruginosa , and Escherichia coli . Minimum inhibitory concentration (MIC) values determined by broth microdilution ranged from 250 to 500 µg/ml, and minimum bactericidal concentration (MBC) values ranged from 1000 to 2000 µg/ml. Antibacterial activity assessed by the well diffusion method was dose-dependent, with inhibition zones ranging from 18 to 28 mm. The effect of MgO NPs on biofilm formation and eradication of pre-formed biofilms was evaluated using microtiter plate assay with crystal violet staining. Percentage inhibition of biofilm formation ranged from 27 to 97.1%, while eradication of established biofilms ranged from 51.9 to 96.4%. Exposure to sub-inhibitory concentrations of MgO NPs led to a 2 to 3-fold increase in reactive oxygen species (ROS) production in treated cells compared to controls. MgO NPs also significantly reduced the protein, carbohydrate, and DNA content of the biofilm matrix. Swimming, swarming, and twitching motility were markedly reduced in treated isolates. Congo red agar assay confirmed that slime production was inhibited following NP treatment. These findings suggest that biogenically synthesized MgO NPs hold considerable promise as antibacterial and antibiofilm agents against MDR Gram-negative pathogens.