Identification of Enhanced Vaccine Mimotopes for the p15E Murine Cancer Antigen.

Unlabelled: Mimotopes of short CD8+ T-cell epitopes generally comprise one or more mutated residues, and can increase the immunogenicity and function of peptide cancer vaccines. We recently developed a two-step approach to generate enhanced mimotopes using positional peptide microlibraries and herein applied this strategy to the broadly used H-2Kb-restricted murine leukemia p15E tumor rejection epitope. The wild-type p15E epitope (sequence: KSPWFTTL) was poorly immunogenic in mice, even when combined with a potent peptide nanoparticle vaccine system and did not delay p15E-expressing MC38 tumor growth.

Folate-Targeted Nanoliposomal Chemophototherapy.

Light-responsive liposomes have been developed for the on-demand release of drugs. However, efficient delivery of chemotherapeutic drugs to tumor for cancer theranostics remains a challenge. Herein, folic acid (FA), an established ligand for targeted drug delivery, was used to decorate light-sensitive porphyrin-phospholipid (PoP) liposomes, which were assessed for FA-targeted chemophototherapy (CPT).

Topical Drug Delivery of Concentrated Cabazitaxel in an α-Tocopherol and DMSO Solution.

Topical chemotherapy approaches are relevant for certain skin cancer treatments. This study observes that cabazitaxel (CTX), a broad-spectrum second-generation taxane cytotoxic agent, can be dissolved in α-tocopherol at high concentrations exceeding 100 mg mL . 2D nuclear magnetic resonance (NMR) analysis and molecular dynamics (MD) are used to study this phenomenon.

Intraperitoneal administration for sustained photoacoustic contrast agent imaging.

Photoacoustic (PA) imaging at 1064 nm in the second near-infrared (NIR-II) has attracted recent attention. We recently reported a surfactant-based formulation of a NIR-II dye (BIBDAH) for NIR-II PA contrast. Here, we investigated BIBDAH as a NIR-II PA contrast agent for longitudinal preclinical PA imaging.

An In Vivo Screen to Identify Short Peptide Mimotopes with Enhanced Antitumor Immunogenicity.

Tumor-associated self-antigens are potential cancer vaccine targets but suffer from limited immunogenicity. There are examples of mutated, short self-peptides inducing epitope-specific CD8+ T cells more efficiently than the wild-type epitope, but current approaches cannot yet reliably identify such epitopes, which are referred to as enhanced mimotopes ("e-mimotopes"). Here, we present a generalized strategy to develop e-mimotopes, using the tyrosinase-related protein 2 (Trp2) peptide Trp2180-188, which is a murine MHC class I (MHC-I) epitope, as a test case.

Immunization with short peptide particles reveals a functional CD8 T-cell neoepitope in a murine renal carcinoma model.

Background: Induction of CD8 T cells that recognize immunogenic, mutated protein fragments in the context of major histocompatibility class I (MHC-I) is a pressing challenge for cancer vaccine development.

Methods: Using the commonly used murine renal adenocarcinoma RENCA cancer model, MHC-I restricted neoepitopes are predicted following next-generation sequencing. Candidate neoepitopes are screened in mice using a potent cancer vaccine adjuvant system that converts short peptides into immunogenic nanoparticles.

Lyophilized, thermostable Spike or RBD immunogenic liposomes induce protective immunity against SARS-CoV-2 in mice.

The COVID-19 pandemic has spurred interest in potent and thermostable SARS-CoV-2 vaccines. Here, we assess low-dose immunization with lyophilized nanoparticles decorated with recombinant SARS-CoV-2 antigens. The SARS-CoV-2 Spike glycoprotein or its receptor-binding domain (RBD; mouse vaccine dose, 0.

Position-Scanning Peptide Libraries as Particle Immunogens for Improving CD8 T-Cell Responses.

Short peptides reflecting major histocompatibility complex (MHC) class I (MHC-I) epitopes frequently lack sufficient immunogenicity to induce robust antigen (Ag)-specific CD8 T cell responses. In the current work, it is demonstrated that position-scanning peptide libraries themselves can serve as improved immunogens, inducing Ag-specific CD8 T cells with greater frequency and function than the wild-type epitope. The approach involves displaying the entire position-scanning library onto immunogenic nanoliposomes.

HPV-Associated Tumor Eradication by Vaccination with Synthetic Short Peptides and Particle-Forming Liposomes.

Human papilloma virus (HPV)-16 is associated with cervical cancers and induces expression of the E6 and E7 oncogenes. Using a murine cell line that expresses these, the genes are sequenced, and six predicted major histocompatibility complex (MHC) class I (MHC-I) epitopes are identified. A liposomal vaccine adjuvant based on cobalt-porphyrin-phospholipid (CoPoP) is admixed with synthetic 9-mer epitopes appended with three histidine residues, resulting in rapid formation of peptide-liposome particles.

Facile formulation of a long-wavelength cyanine for optical imaging in the second near-infrared window.

The second near-infrared window (NIR-II) beyond 1000 nm has attracted attention for optical contrast imaging in small animals. We sought to assess whether commercially available NIR-II dyes could be easily formulated for this purpose. 13 hydrophobic NIR-II dyes were purchased and screened by formulating them in simple solubilizing agents with established use in humans: propylene glycol, Cremaphor EL, Kolliphor HS15 (HS15), Tween 80, and cyclodextrin.

Natriuretic Peptide Receptor 2 Locus Contributes to Carotid Remodeling.

Background Carotid artery intima/media thickness (IMT) is a hallmark trait associated with future cardiovascular events. The goal of this study was to map new genes that regulate carotid IMT by genome-wide association. Methods and Results We induced IMT by ligation procedure of the left carotid artery in 30 inbred mouse strains.

The Protective Role of Natriuretic Peptide Receptor 2 against High Salt Injury in the Renal Papilla.

Mutations in natriuretic peptide receptor 2 (Npr2) gene cause a rare form of short-limbed dwarfism, but its physiological effects have not been well studied. Human and mouse genetic data suggest that Npr2 in the kidney plays a role in salt homeostasis. Herein, we described anatomic changes within renal papilla of Npr2 knockout (Npr2) mice.

Strain-selective efficacy of sacubitril/valsartan on carotid fibrosis in response to injury in two inbred mouse strains.

Background And Purpose: Sacubitril/valsartan (Sac/val) is more effective than valsartan in lowering BP and mortality in patients with heart failure. Here, we proposed that Sac/val treatment would be more effective in preventing pathological vascular remodelling in 129X1/SvJ (129X1), than in C57BL/6J (B6) inbred mice.

Experimental Approach: Sac/val (60 mg·kg ·day ) and valsartan (27 mg·kg ·day ) were given as prophylactic or therapeutic treatments, to 129X1 or B6 mice with carotid artery ligation for 14 days.

Transglutaminase 2: Friend or foe? The discordant role in neurons and astrocytes.

Members of the transglutaminase family catalyze the formation of isopeptide bonds between a polypeptide-bound glutamine and a low molecular weight amine (e.g., spermidine) or the ɛ-amino group of a polypeptide-bound lysine.