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    Advances and Challenges in Interventional Immuno-Oncology Locoregional Therapies
    (Elsevier Science Inc, 2024) Altun, Izzet; Demirlenk, Yusuf M.; Atar, Dila; Cevik, Enes; Gunduz, Seyda; Albadawi, Hassan; Oklu, Rahmi
    Interventional immuno-oncology is making strides in locoregional therapies to address complex tumor microenvironments. Long-standing interventional radiology cancer therapies, such as tumor ablation and embolization, are being recharacterized in the context of immunotherapy. Intratumoral injections, such as those of genetically engineered or unaltered viruses, and the delivery of immune cells, antibodies, proteins, or cytokines into targeted tumors, along with advancements in delivery techniques, have produced promising results in preliminary studies, indicating their antitumor effectiveness. Emerging strategies using DNA scaffolding, polysaccharides, glycan, chitosan, and natural products are also showing promise in targeted cancer therapy. The future of interventional immuno-oncology lies in personalized immunotherapies that capitalize on individual immune profiles and tumor characteristics, along with the exploration of combination therapies. This study will review various interventional immuno-oncology strategies and emerging technologies to enhance delivery of therapeutics and response to immunotherapy.
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    Prostate tissue ablation and drug delivery by an image-guided injectable ionic liquid in ex vivo and in vivo models
    (American association advancement science, 2024) Demirlenk, Yusuf M.; Albadawi, Hassan; Zhang, Zefu; Atar, Dila; Çevik, Enes; Keum, Hyeongseop; Kim, Jinjoo; Rehman, Suliman; Gündüz, Şeyda; Graf, Erin; Mayer, Joseph L.; Dos Santos, Pedro R.; Oklu, Rahmi
    Benign prostatic hyperplasia and prostate cancer are often associated with lower urinary tract symptoms, which can severely affect patient quality of life. To address this challenge, we developed and optimized an injectable compound, prostate ablation and drug delivery agent (PADA), for percutaneous prostate tissue ablation and concurrently delivered therapeutic agents. PADA is an ionic liquid composed of choline and geranic acid mixed with anticancer therapeutics and a contrast agent. The PADA formulation was optimized for mechanical properties compatible with hand injection, diffusion capability, cytotoxicity against prostate cells, and visibility of an x-ray contrast agent. PADA also exhibited antibacterial properties against highly resistant clinically isolated bacteria in vitro. Ultrasound-guided injection, dispersion of PADA in the tissue, and tissue ablation were tested ex vivo in healthy porcine, canine, and human prostates and in freshly resected human tumors. In vivo testing was conducted in a murine subcutaneous tumor model and in the canine prostate. In all models, PADA decreased the number of viable cells in the region of dispersion and supported the delivery of nivolumab throughout a portion of the tissue. In canine survival experiments, there were no adverse events and no impact on urination. The injection approach was easy to perform under ultrasound guidance and produced a localized effect with a favorable safety profile. These findings suggest that PADA is a promising therapeutic prostate ablation strategy to treat lower urinary tract symptoms.