TY - JOUR T1 - In situ delivery of nanoparticles formulated with micron-sized crystals protects from murine melanoma JF - Journal for ImmunoTherapy of Cancer JO - J Immunother Cancer DO - 10.1136/jitc-2022-004643 VL - 10 IS - 9 SP - e004643 AU - Mona O Mohsen AU - Matthew Heath AU - Matthias F Kramer AU - Thalia Carreno Velazquez AU - Alan Bullimore AU - Murray A Skinner AU - Daniel E Speiser AU - Martin F Bachmann Y1 - 2022/09/01 UR - http://jitc.bmj.com/content/10/9/e004643.abstract N2 - Introduction Intratumoral injections of novel therapeutics can activate tumor antigen-specific T cells for locoregional tumor control and may even induce durable systemic protection (against distant metastases) via recirculating T cells. Here we explored the possibility of a universal immunotherapy that promotes T-cell responses in situ and beyond, upon intratumoral injection of nanoparticles formulated with micron-sized crystals.Methods Cucumber mosaic virus-like particles containing a tetanus toxin peptide (CuMVTT) were formulated with microcrystalline tyrosine (MCT) adjuvant and injected directly in B16F10 melanoma tumors. To further enhance immunogenicity, we loaded the nanoparticles with a TLR7/8 ligand and incorporated a universal tetanus toxin T-helper cell peptide. We assessed therapeutic efficacy and induction of local and systemic immune responses, including RNA sequencing, providing broad insight into the tumor microenvironment and correlates of protection.Results MCT crystals were successfully decorated with CuMVTT nanoparticles. This ‘immune-enhancer’ formed immunogenic depots in injected tumors, enhanced polyfunctional CD8+ and CD4+ T cells, and inhibited B16F10 tumor growth locally and systemically. Local inflammation and immune responses were associated with upregulation of genes involved in complement activation and collagen formation.Conclusions Our new immune-enhancer turned immunologically cold tumors into hot ones and inhibited local and distant tumor growth. This type of immunotherapy does not require the identification of (patient–individual) relevant tumor antigens. It is well tolerated, non-infectious, and affordable, and can readily be upscaled for future clinical testing and broad application in melanoma and likely other solid tumors.Data are available upon reasonable request. Data are available upon request. ER -