In this study, a novel type of matrix with regular nanotopography composed of crosslinked carbon nanotubes is used as a cell‐growing scaffold. The cytocompatibility of this matrix and cell–surface ...interaction is assessed using human osteoblast cells (HOBs). The growth behavior of HOB cells, including morphology, metabolic activity and adhesion are explored by means of scanning electron microscopy and cell viability assay. Additionally, atomic force microscopy is used to evaluate the biocompatibility of carbon nanotube (CNT)‐based scaffolds by investigating the adhesion behavior of attached cells. The elastic properties of living osteoblast on the matrices with a unique cavity‐like topography are compared with cells adhered to the glass and randomly‐distributed CNTs. The elevated Young's modulus of matrices with regular topography suggests the presence of tight junctions and a high‐quality adhesion mechanism, which in turn indicates good biocompatibility of the matrices.
A novel, highly ordered MWCNT‐based matrix, engineered with biologically important nanoscaled topography is explored as a scaffold for osteoblast cell growth. The exceptional nanotopography of the matrices provides enhanced cell adhesion, which is confirmed by scanning electron microscopy observation and atomic force microscopy nanomechanical analysis.
T cells directed against mutant neo-epitopes drive cancer immunity. However, spontaneous immune recognition of mutations is inefficient. We recently introduced the concept of individualized mutanome ...vaccines and implemented an RNA-based poly-neo-epitope approach to mobilize immunity against a spectrum of cancer mutations. Here we report the first-in-human application of this concept in melanoma. We set up a process comprising comprehensive identification of individual mutations, computational prediction of neo-epitopes, and design and manufacturing of a vaccine unique for each patient. All patients developed T cell responses against multiple vaccine neo-epitopes at up to high single-digit percentages. Vaccine-induced T cell infiltration and neo-epitope-specific killing of autologous tumour cells were shown in post-vaccination resected metastases from two patients. The cumulative rate of metastatic events was highly significantly reduced after the start of vaccination, resulting in a sustained progression-free survival. Two of the five patients with metastatic disease experienced vaccine-related objective responses. One of these patients had a late relapse owing to outgrowth of β2-microglobulin-deficient melanoma cells as an acquired resistance mechanism. A third patient developed a complete response to vaccination in combination with PD-1 blockade therapy. Our study demonstrates that individual mutations can be exploited, thereby opening a path to personalized immunotherapy for patients with cancer.
One of the major problems associated with the development of a vaccine against
Streptococcus pyogenes is the ability of this pathogen to escape recognition by antibodies directed against conserved ...surface-associated determinants and to establish infection in the setting of an acquired immune response. Identification of the mechanism(s) used by
S. pyogenes to avoid recognition by antigen-specific antibodies and escape killing in blood was the focus of this study. We showed here that
S. pyogenes was capable of surviving in human blood containing high levels of antibodies directed against the G-related α
2-macroglobulin-binding protein GRAB, a highly conserved bacterial surface protein.
S. pyogenes upregulated the hyaluronic acid capsule production during incubation with human blood, suggesting that the capsule may structurally minimize antibody access to protein GRAB. This hypothesis was confirmed by the ability of anti-GRAB antibodies to promote opsonophagocytosis of a capsule-deficient mutant of
S. pyogenes but not of the encapsulated wild-type strain. Capsule upregulation and protection of
S. pyogenes from opsonophagocytosis in the presence of anti-GRAB antibodies was also observed in a murine model of streptococcal infection. Thus, masking of surface immunogenic determinants by the hyaluronic acid capsule may constitute a novel mechanism of
S. pyogenes for evasion of antigen-specific antibodies.
One of the major problems associated with the development of a vaccine against Streptococcus pyogenes is the ability of this pathogen to escape recognition by antibodies directed against conserved ...surface-associated determinants and to establish infection in the setting of an acquired immune response. Identification of the mechanism(s) used by S. pyogenes to avoid recognition by antigen-specific antibodies and escape killing in blood was the focus of this study. We showed here that S. pyogenes was capable of surviving in human blood containing high levels of antibodies directed against the G-related alpha2-macroglobulin-binding protein GRAB, a highly conserved bacterial surface protein. S. pyogenes upregulated the hyaluronic acid capsule production during incubation with human blood, suggesting that the capsule may structurally minimize antibody access to protein GRAB. This hypothesis was confirmed by the ability of anti-GRAB antibodies to promote opsonophagocytosis of a capsule-deficient mutant of S. pyogenes but not of the encapsulated wild-type strain. Capsule upregulation and protection of S. pyogenes from opsonophagocytosis in the presence of anti-GRAB antibodies was also observed in a murine model of streptococcal infection. Thus, masking of surface immunogenic determinants by the hyaluronic acid capsule may constitute a novel mechanism of S. pyogenes for evasion of antigen-specific antibodies.
