Therapeutic vaccines are a promising alternative for active immunotherapy for different types of cancers. Therapeutic cancer vaccines aim to prevent immune system responses that are not targeted at the tumors only, but also boost the anti-tumor immunity and promote regression or eradication of the malignancy without, or with minimal, adverse events. Clinical trial data have pushed the development of cancer vaccines forward, and the US Food and Drug Administration authorized the first therapeutic cancer vaccine. In the present review, we discuss the various types of cancer vaccines and different approaches for the development of therapeutic cancer vaccines, along with the current state of knowledge and future prospects. We also discuss how tumor-induced immune suppression limits the effectiveness of therapeutic vaccinations, and strategies to overcome this barrier to design efficacious, long-lasting anti-tumor immune responses in the generation of vaccines.

Chronic infections often involve notorious pathogens like Pseudomonas aeruginosa and Staphylococcus aureus, demanding innovative antimicrobial strategies due to escalating resistance. This investigation scrutinized the antibacterial prowess of bile salts, notably taurocholic acid (TCA), ursodeoxycholic acid (UDCA), and ox bile salt (OBS), against these pathogens. Evaluations encompassed minimum inhibitory concentration (MIC) determination, scrutiny of their impact on biofilm formation, and anti-virulence mechanisms. UDCA exhibited the highest efficacy, suppressing S. aureus and P. aeruginosa biofilms by 83.5% and 78%, respectively, at peak concentration. TCA also significantly reduced biofilm development by 81% for S. aureus and 75% for P. aeruginosa. Microscopic analysis revealed substantial disruption of biofilm architecture by UDCA and TCA. Conversely, OBS demonstrated ineffectiveness against both pathogens. Mechanistic assays elucidated UDCA and TCA’s detrimental impact on the cell membrane, prompting the release of macromolecular compounds. Additionally, UDCA and TCA inhibited protease and elastase synthesis in P. aeruginosa and staphyloxanthin and lipase production in S. aureus. These results underscore the potential of UDCA and TCA in impeding biofilm formation and mitigating the pathogenicity of S. aureus and P. aeruginosa.

Chronic infections pose significant clinical challenges due to their persistent nature, heightened resistance to conventional therapies, and association with biofilm formation. Neutrophil extracellular traps (NETs), released through a unique form of cell death known as NETosis, serve as an innate immune defense mechanism by trapping and neutralizing pathogens. However, accumulating evidence reveals a complex and paradoxical relationship between NETs and microbial biofilms. While NETs can immobilize and kill planktonic microbes, the extracellular DNA and associated proteins often contribute to biofilm stability, immune evasion, and chronic infection persistence. This review explores the bidirectional interactions between NETosis and biofilm formation, with a focus on their synergistic roles in the pathogenesis of chronic infections such as cystic fibrosis lung disease, diabetic foot ulcers, periodontitis, and implant-associated infections. We outline the molecular mechanisms governing NETosis, the structural and functional dynamics of biofilms, and how these processes intersect to form recalcitrant infection niches. Emerging therapeutic strategies aimed at disrupting this pathogenic interplay including DNase-based treatments, PAD4 inhibitors, and combination therapies are critically evaluated. By illuminating the pathogenic synergy between NETs and biofilms, this review underscores the need for integrated immunomodulatory and anti-biofilm interventions to effectively manage chronic infectious diseases and improve patient outcomes.

Staphylococcus aureus is a biofilm-forming bacterium responsible for various human infections, one particularly challenging to treat due to its antibiotic resistance. Biofilms can form on both soft tissues and medical devices, leading to persistent and hard-to-treat infections. Combining multiple antimicrobials is a potential approach to overcoming this resistance. This study explored the effects of ursodeoxycholic acid (UDCA) combined with the antibiotic ciprofloxacin against S. aureus biofilms, aiming to evaluate any synergistic effects. Results showed that UDCA and ciprofloxacin co-treatment significantly reduced biofilm formation and disrupted pre-formed biofilms more effectively than either agent alone (p < 0.01). The combination also displayed a slight synergistic effect, with a fractional inhibitory concentration of 0.65. Additionally, the treatment reduced the production of extracellular polymeric substances, increased reactive oxygen species production, decreased metabolic activity, altered cell membrane permeability, and lowered cell surface hydrophobicity in S. aureus. Furthermore, it diminished biofilm-associated pathogenic factors, including proteolytic activity and staphyloxanthin production. Overall, the UDCA–ciprofloxacin combination shows considerable promise as a strategy to combat infections related to staphylococcal biofilms, offering a potential solution to the healthcare challenges posed by antibiotic-resistant S. aureus.