Design and selection of anti-PD-L1 single-domain antibody and tumor necrosis factor superfamily ligands for an optimal vectorization in an oncolytic virus.

Arming oncolytic viruses with transgenes encoding immunomodulators improves their therapeutic efficacy by enhancing and/or sustaining the innate and adaptive anti-tumoral immune responses. We report here the isolation, selection, and vectorization of a blocking anti-human PDL1 single-domain antibody (sdAb) isolated from PDL1-immunized alpacas. Several formats of this sdAb were vectorized into the vaccinia virus (VV) and evaluated for their programmed cell death protein 1 (PD1)/PD1 ligand (PDL1) blocking activity in the culture medium of tumor cells infected .

Meniscal injuries in skeletally immature children with tibial eminence fractures. Systematic review of literature.

Purpose: Although the mechanisms of injury are similar to ACL rupture in adults, publications dealing with meniscal lesions resulting from fractures of the intercondylar eminence in children are much rarer. The main objective was to measure the frequency of meniscal lesions associated with tibial eminence fractures in children. The second question was to determine whether there is any available evidence on association between meniscal tears diagnostic method, and frequencies of total lesions, total meniscal lesions, and total entrapments.

A novel virotherapy encoding human interleukin-7 improves T lymphocyte functions in immunosuppressed patients with septic shock and critically ill COVID-19.

A majority of patients with sepsis surviving the first days in intensive care units (ICU) enter a state of immunosuppression contributing to their worsening. A novel virotherapy based on the non-propagative Modified Virus Ankara (MVA) expressing the human interleukin-7 (hIL-7) cytokine fused to an Fc fragment, MVA-hIL-7-Fc, was developed and shown to enhance innate and adaptive immunity and confer survival advantages in murine sepsis models. Here, we assessed the capacity of hIL-7-Fc produced by the MVA-hIL-7-Fc to improve T lymphocyte functions from ICU patients with sepsis.

Viral Delivery of IL-7 Is a Potent Immunotherapy Stimulating Innate and Adaptive Immunity and Confers Survival in Sepsis Models.

Persistence of an immunosuppressive state plays a role in septic patient morbidity and late mortality. Both innate and adaptive pathways are impaired, pointing toward the need for immune interventions targeting both arms of the immune system. We developed a virotherapy using the nonpropagative modified vaccinia virus Ankara (MVA), which harbors the intrinsic capacity to stimulate innate immunity, to deliver IL-7, a potent activator of adaptive immunity.

Transsexualism and transgenderism: Unravelling sex and gender, and abstractions of the sexed body.

Although transgenderism is accorded an increasingly important place at the heart of studies concerning problems of gender nonconformity, it remains a phenomenon that is poorly known, and difficult to define, in particular in its relationship with transsexualism. In fact, in spite of an undeniable kinship between them, these two phenomena can be distinguished one from the other, and each represents a way of relating to the subject of the difference between the sexes. To clarify this subject, this article initially presents their emergence, their commonalities and their differences from a historical point of view.

By Binding CD80 and CD86, the Vaccinia Virus M2 Protein Blocks Their Interactions with both CD28 and CTLA4 and Potentiates CD80 Binding to PD-L1.

In this article we report that the M2 protein encoded by the vaccinia virus is secreted as a homo-oligomer by infected cells and binds two central costimulation molecules, CD80 (B7-1) and CD86 (B7-2). These interactions block the ligation of the two B7 proteins to both soluble CD28 and soluble cytotoxic T-lymphocyte associated protein 4 (CTLA4) but favor the binding of soluble PD-L1 to soluble CD80. M2L gene orthologues are found in several other poxviruses, and the B7-CD28/CTLA4 blocking activity has been identified for several culture supernatants of orthopoxvirus-infected cells and for a recombinant myxoma virus M2 protein homolog (i.

A multi-antigenic MVA vaccine increases efficacy of combination chemotherapy against Mycobacterium tuberculosis.

Despite the existence of the prophylactic Bacille Calmette-Guérin (BCG) vaccine, infection by Mycobacterium tuberculosis (Mtb) remains a major public health issue causing up to 1.8 million annual deaths worldwide. Increasing prevalence of Mtb strains resistant to antibiotics represents an urgent threat for global health that has prompted a search for alternative treatment regimens not subject to development of resistance.

Vectorization in an oncolytic vaccinia virus of an antibody, a Fab and a scFv against programmed cell death -1 (PD-1) allows their intratumoral delivery and an improved tumor-growth inhibition.

We report here the successful vectorization of a hamster monoclonal IgG (namely J43) recognizing the murine Programmed cell death-1 (mPD-1) in Western Reserve (WR) oncolytic vaccinia virus. Three forms of mPD-1 binders have been inserted into the virus: whole antibody (mAb), Fragment antigen-binding (Fab) or single-chain variable fragment (scFv). MAb, Fab and scFv were produced and assembled with the expected patterns in supernatants of cells infected by the recombinant viruses.

A Novel MVA-Based Multiphasic Vaccine for Prevention or Treatment of Tuberculosis Induces Broad and Multifunctional Cell-Mediated Immunity in Mice and Primates.

Bacille Calmette-Guérin (BCG) vaccination of new born babies can protect children against tuberculosis (TB), but fails to protect adults consistently against pulmonary TB underlying the urgent need to develop novel TB vaccines. Majority of first generation TB vaccine candidates have relied on a very limited number of antigens typically belonging to the active phase of infection. We have designed a multi-antigenic and multiphasic vaccine, based on the Modified Vaccinia Ankara virus (MVA).

Do graft diameter or patient age influence the results of ACL reconstruction?

Purpose: Hamstring tendons are commonly used as a graft source for ACL reconstruction. This study seeks to determine whether either the diameter of the tendon graft or the age of the patient influences the outcome of the ACL reconstruction when measured using a standard, previously validated laxity measurement device.

Methods: This is a retrospective study of 88 patients who underwent ACL reconstruction with a short, quadrupled tendon technique, using the semitendinosus ± gracilis tendons.

TG1050, an immunotherapeutic to treat chronic hepatitis B, induces robust T cells and exerts an antiviral effect in HBV-persistent mice.

Objective: To assess a new adenovirus-based immunotherapy as a novel treatment approach to chronic hepatitis B (CHB).

Methods: TG1050 is a non-replicative adenovirus serotype 5 encoding a unique large fusion protein composed of a truncated HBV Core, a modified HBV Polymerase and two HBV Envelope domains. We used a recently described HBV-persistent mouse model based on a recombinant adenovirus-associated virus encoding an over length genome of HBV that induces the chronic production of HBsAg, HBeAg and infectious HBV particles to assess the ability of TG1050 to induce functional T cells in face of a chronic status.

Yeast virus-derived stimulator of the innate immune system augments the efficacy of virus vector-based immunotherapy.

Unlabelled: To identify novel stimulators of the innate immune system, we constructed a panel of eight HEK293 cell lines double positive for human Toll-like receptors (TLRs) and an NF-κB-inducible reporter gene. Screening of a large variety of compounds and cellular extracts detected a TLR3-activating compound in a microsomal yeast extract. Fractionation of this extract identified an RNA molecule of 4.

Posttraumatic axillary false aneurysm after luxatio erecta of the shoulder: case report and literature review.

Vascular complications after dislocation of the shoulder are rare. We report a case of glenohumeral inferior dislocation (luxatio erecta) responsible for an acute ischemia of the upper limb. Endovascular treatment with a covered stent associated with the evacuation of the compressive hematoma was privileged.

3D modeling and characterization of the human CD115 monoclonal antibody H27K15 epitope and design of a chimeric CD115 target.

The humanized monoclonal antibody H27K15 specifically targets human CD115, a type III tyrosine kinase receptor involved in multiple cancers and inflammatory diseases. Binding of H27K15 to hCD115 expressing cells inhibits the functional effect of colony-stimulating factor-1 (CSF-1), in a non-competitive manner. Both homology modeling and docking programs were used here to model the human CD115 extracellular domains, the H27K15 variable region and their interaction.

Therapeutic effects of anti-CD115 monoclonal antibody in mouse cancer models through dual inhibition of tumor-associated macrophages and osteoclasts.

Tumor progression is promoted by Tumor-Associated Macrophages (TAMs) and metastasis-induced bone destruction by osteoclasts. Both myeloid cell types depend on the CD115-CSF-1 pathway for their differentiation and function. We used 3 different mouse cancer models to study the effects of targeting cancer host myeloid cells with a monoclonal antibody (mAb) capable of blocking CSF-1 binding to murine CD115.

A unique anti-CD115 monoclonal antibody which inhibits osteolysis and skews human monocyte differentiation from M2-polarized macrophages toward dendritic cells.

Cancer progression has been associated with the presence of tumor-associated M2-macrophages (M2-TAMs) able to inhibit anti-tumor immune responses. It is also often associated with metastasis-induced bone destruction mediated by osteoclasts. Both cell types are controlled by the CD115 (CSF-1R)/colony-stimulating factor-1 (CSF-1, M-CSF) pathway, making CD115 a promising target for cancer therapy.

Safety and efficiency of a 2-portal lateral approach to arthroscopic subtalar arthrodesis: a cadaveric study.

Purpose: To investigate the safety and efficiency of a 2-portal lateral (anterior and middle) approach to arthroscopic subtalar arthrodesis.

Methods: A cadaveric study was performed on 30 feet of 15 fresh cadaveric bodies (15 right and 15 left; 21 female specimens and 9 male specimens). The mean age at death was 78 ± 6.

Solid-state NMR sequential assignments of the C-terminal oligomerization domain of human C4b-binding protein.

The complement 4 binding protein (C4bp) plays a crucial role in the inhibition of the complement cascade. It has an extraordinary seven-arm octopus-like structure with 7 tentacle-like identical chains, held together at their C-terminal end. The C-terminal domain does oligomerize in isolation, and is necessary and sufficient to oligomerize full-length C4bp.

The oligomerization domain of C4-binding protein (C4bp) acts as an adjuvant, and the fusion protein comprised of the 19-kilodalton merozoite surface protein 1 fused with the murine C4bp domain protects mice against malaria.

Highly purified protein antigens are usually poor immunogens; in practice, adjuvants are needed to obtain satisfactory immune responses. Plasmodium yoelii 19-kDa merozoite surface protein 1 (MSP1(19)) is a weak antigen, but mice vaccinated with this antigen in strong adjuvants can survive an otherwise lethal parasite challenge. Fusion proteins comprising this antigen fused to the oligomerization domain of the murine complement inhibitor C4-binding protein (C4bp) and a series of homologues have been produced.

Interactions of WASp, myosin-I, and verprolin with Arp2/3 complex during actin patch assembly in fission yeast.

Yeast actin patches are dynamic structures that form at the sites of cell growth and are thought to play a role in endocytosis. We used biochemical analysis and live cell imaging to investigate actin patch assembly in fission yeast Schizosaccharomyces pombe. Patch assembly proceeds via two parallel pathways: one dependent on WASp Wsp1p and verprolin Vrp1p converges with another dependent on class 1 myosin Myo1p to activate the actin-related protein 2/3 (Arp2/3) complex.