A5076209726- Immunotherapy and Immune Responses
- vaccines and immunoinformatics approaches
- Cancer Research and Treatments
- Monoclonal and Polyclonal Antibodies Research
- Nanoparticle-Based Drug Delivery
- Virus-based gene therapy research
- Nanoplatforms for cancer theranostics
- Photoacoustic and Ultrasonic Imaging
- Cancer Immunotherapy and Biomarkers
- Glycosylation and Glycoproteins Research
- Peptidase Inhibition and Analysis
- Porphyrin and Phthalocyanine Chemistry
- SARS-CoV-2 and COVID-19 Research
- Antimicrobial Peptides and Activities
- Advanced Polymer Synthesis and Characterization
- Spectroscopy Techniques in Biomedical and Chemical Research
- Protein Interaction Studies and Fluorescence Analysis
- Optical Imaging and Spectroscopy Techniques
- CAR-T cell therapy research
- Thermography and Photoacoustic Techniques
- Microtubule and mitosis dynamics
- T-cell and B-cell Immunology
- Photodynamic Therapy Research Studies
- RNA Interference and Gene Delivery
- Advancements in Transdermal Drug Delivery
University at Buffalo, State University of New York
2020-2025
State University of New York
2020
Buffalo BioLabs
2020
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 recombinant antigens. Spike glycoprotein or its receptor-binding domain (RBD; mouse vaccine dose, 0.1 μg) was displayed on liposomes incorporating a particle-inducing lipid, cobalt porphyrin-phospholipid (dose, 0.4 μg), along monophosphoryl lipid A 0.16 QS-21 μg). Following optimization of lyophilization conditions,...
Abstract Human papilloma virus (HPV)‐16 is associated with cervical cancers and induces expression of the E6 E7 oncogenes. Using a murine cell line that expresses these, genes are sequenced, six predicted major histocompatibility complex (MHC) class I (MHC‐I) epitopes identified. A liposomal vaccine adjuvant based on cobalt–porphyrin‐phospholipid (CoPoP) admixed synthetic 9‐mer appended three histidine residues, resulting in rapid formation peptide–liposome particles. Immunization...
Induction of CD8+ T cells that recognize immunogenic, mutated protein fragments in the context major histocompatibility class I (MHC-I) is a pressing challenge for cancer vaccine development.Using commonly used murine renal adenocarcinoma RENCA model, MHC-I restricted neoepitopes are predicted following next-generation sequencing. Candidate screened mice using potent adjuvant system converts short peptides into immunogenic nanoparticles. An identified functional neoepitope then tested...
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
Mimotopes of short CD8+ T-cell epitopes generally comprise one or more mutated residues, and can increase the immunogenicity function peptide cancer vaccines. We recently developed a two-step approach to generate enhanced mimotopes using positional microlibraries herein applied this strategy broadly used H-2Kb-restricted murine leukemia p15E tumor rejection epitope. The wild-type epitope (sequence: KSPWFTTL) was poorly immunogenic in mice, even when combined with potent nanoparticle vaccine...
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 this purpose. 13 hydrophobic were purchased and screened by formulating them simple solubilizing agents with established use humans: propylene glycol, Cremaphor EL, Kolliphor HS15 (HS15), Tween 80, cyclodextrin. Based on the absorption at 1064 (matching Nd:YAG laser output...
Tumor-associated self-antigens are potential cancer vaccine targets but suffer from limited immunogenicity. There examples of mutated, short self-peptides inducing epitope-specific CD8+ T cells more efficiently than the wild-type epitope, current approaches cannot yet reliably identify such epitopes, which referred to as enhanced mimotopes ("e-mimotopes"). Here, we present a generalized strategy develop e-mimotopes, using tyrosinase-related protein 2 (Trp2) peptide Trp2180-188, is murine MHC...
Light-responsive liposomes have been developed for the on-demand release of drugs. However, efficient delivery chemotherapeutic drugs to tumor cancer theranostics remains a challenge. Herein, folic acid (FA), an established ligand targeted drug delivery, was used decorate light-sensitive porphyrin-phospholipid (PoP) liposomes, which were assessed FA-targeted chemophototherapy (CPT). PoP and FA-conjugated loaded with Doxorubicin (Dox), physical properties characterized. In vitro, FA-PoP that...
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 cells with greater frequency and function than wild-type epitope. The approach involves displaying entire library onto immunogenic nanoliposomes. Each...
<p>p15E-3C2V immunized mice showed long-term resistance to MC38 tumor re-challenge</p>
<div>Abstract<p>Mimotopes of short CD8<sup>+</sup> T-cell epitopes generally comprise one or more mutated residues, and can increase the immunogenicity function peptide cancer vaccines. We recently developed a two-step approach to generate enhanced mimotopes using positional microlibraries herein applied this strategy broadly used H-2K<sup>b</sup>–restricted murine leukemia p15E tumor rejection epitope. The wild-type epitope (sequence: KSPWFTTL) was poorly...
<p>The wild-type p15E short peptide is poorly immunogenic and does not inhibit tumor growth. C57BL/6 mice were vaccinated intramuscularly with 2 μg of E7 or displayed on CPQ liposomes (along 8 CoPoP, 3.2 PHAD QS-21) day 0 7; then blood was collected for Ag-specific CD8<sup>+</sup> T-cell tetramer staining 14 challenged 1 × 10<sup>5</sup> TC-1 cells 10<sup>6</sup> MC38 cells. (<b>A</b>) percentages in T blood. (<b>B</b>)...
<p>Functional screening of positional peptide microlibraries reveals 3M and 3C substitutions as p15E e-mimotopes. <b>A,</b> Schematic shows the strategy two-step e-mimotope screening. Mice were vaccinated with position library vaccines (<b>B</b>) or individual (<b>C</b>) 3 amino acid being replaced, indicated. Vaccinations occurred on days 0 day 7, followed by inoculation 1 × 10<sup>6</sup> MC38 cells 14. Tumor volume 19 after tumor was...
<p>The p15E-3M mimotope induces improved cytotoxic T-cell responses <i>in vitro</i>. <b>A,</b> Mean fluorescence intensity (MFI) of the indicated peptides bound to RMA-S cells after staining with PE-labeled anti-mouse H-2K<sup>b</sup> antibody. <b>B,</b> Binding stability peptide MHC-I molecules. Mice were immunized 2 µg liposomal vaccine per injection on days 0 and day 7. <b>C</b>, The percentage p15E-specific...
<p>The p15E-3M mimotope induces improved cytotoxic T-cell responses <i>in vitro</i>. <b>A,</b> Mean fluorescence intensity (MFI) of the indicated peptides bound to RMA-S cells after staining with PE-labeled anti-mouse H-2K<sup>b</sup> antibody. <b>B,</b> Binding stability peptide MHC-I molecules. Mice were immunized 2 µg liposomal vaccine per injection on days 0 and day 7. <b>C</b>, The percentage p15E-specific...
<p>Efficacy of p15E-3C and p15E-3M e-mimotope vaccines at submicrogram peptide doses in prophylactic therapeutic MC38 tumor challenges. Mice were immunized intramuscularly with CPQ liposomes containing 0.8 µg PHAD, QS-21, 0.5 p15E wild-type, p15-3C, or p15-3M on days 0 7 challenged 1 × 10<sup>6</sup> MC-38 cells subcutaneously day 14 (<i>n</i> = 5 mice per group). Individual volumes (<b>A</b>) the percentage length under 10 mm (<b>B</b>)....
<p>TCR sequencing of wild-type p15E-specific CD8 T cells sorted from splenocytes 3C, 3M, and 3C2V immunized mice. <b>A,</b> Percentage Ag-specific CD8<sup>+</sup> in all cells. <b>B,</b> Proportion total repertoire occupied by top 30 most abundance clonotypes. The peptide vaccine dose (in µg) used to induce is shown below the graph. <b>C,</b> Length distribution observed CDR3 amino acid sequences within each sample. Lines represent mean...
<p>Flow cytometry cell gating strategy</p>
<p>TCR sequencing of wild-type p15E-specific CD8 T cells sorted from splenocytes 3C, 3M, and 3C2V immunized mice. <b>A,</b> Percentage Ag-specific CD8<sup>+</sup> in all cells. <b>B,</b> Proportion total repertoire occupied by top 30 most abundance clonotypes. The peptide vaccine dose (in µg) used to induce is shown below the graph. <b>C,</b> Length distribution observed CDR3 amino acid sequences within each sample. Lines represent mean...
<p>CD8+ or CD4+ T cell depletion with murine anti-CD8 anti-CD4 monoclonal antibodies</p>
<p>CD8+ or CD4+ T cell depletion with murine anti-CD8 anti-CD4 monoclonal antibodies</p>