Rates of Positive Aspiration Prior to Facial Hyaluronic Acid Filler Injections: Outcomes of a Multicenter, Cross-Sectional Study.

Background: Before administering hyaluronic acid (HA) fillers, aspiration can be performed as a safety measure to verify whether the needle tip is possibly located within a vascular structure. However, the efficacy and utility of aspiration have been questioned. A real-world evaluation would contribute to the literature and understanding of how this technique is used globally.

An automated and high-throughput approach for enhanced precision of adenoviral titering.

Accurate quantification of viral vectors and vaccines is a crucial step required before any downstream use of virus preparations. The conventional immunocytochemistry-based method of adenovirus quantification has been widely used, but there are many areas for improvement toward accuracy and resource consumption savings to reduce viral miscalculation and wastage of vaccination materials. In this work, a one-step approach is implemented for optimized adenoviral quantification that uses a single antibody coupled with automated, high-throughput image acquisition and subsequent batch analysis.

Transdermal delivery of PeptiCRAd cancer vaccine using microneedle patches.

Microneedles (MNs) are a prospective system in cancer immunotherapy to overcome barriers regarding proper antigen delivery and presentation. This study aims at identifying the potential of MNs for the delivery of Peptide-coated Conditionally Replicating Adenoviruses (PeptiCRAd), whereby peptides enhance the immunogenic properties of adenoviruses presenting tumor associated antigens. The combination of PeptiCRAd with MNs containing polyvinylpyrrolidone and sucrose was tested for the preservation of structure, induction of immune response, and tumor eradication.

Low-dose decitabine enhances the efficacy of viral cancer vaccines for immunotherapy.

Cancer immunotherapy requires a specific antitumor CD8 T cell-driven immune response; however, upon genetic and epigenetic alterations of the antigen processing and presenting components, cancer cells escape the CD8 T cell recognition. As a result, poorly immunogenic tumors are refractory to conventional immunotherapy. In this context, the use of viral cancer vaccines in combination with hypomethylating agents represents a promising strategy to prevent cancer from escaping immune system recognition.

Novel peptide-based oncolytic vaccine for enhancement of adaptive antitumor immune response via co-engagement of innate Fcγ and Fcα receptors.

Background: Cancer immunotherapy relies on using the immune system to recognize and eradicate cancer cells. Adaptive immunity, which consists of mainly antigen-specific cytotoxic T cells, plays a pivotal role in controlling cancer progression. However, innate immunity is a necessary component of the cancer immune response to support an immunomodulatory state, enabling T-cell immunosurveillance.

Simplifying the injector's armamentarium: An international consensus regarding the use of gel science to differentiate hyaluronic acid fillers and guide treatment recommendations.

Background: The Restylane portfolio of soft tissue fillers spans a wide range of indications, due in part to their complementary manufacturing technologies [non-animal stabilized hyaluronic acid (NASHA) and Optimal Balance Technology (OBT/XpresHAn)]. Using an array of products, injectors can achieve a holistic, natural looking effect for their patients. However, with a wide range of products it may be difficult to choose an optimal combination.

Development of mesothelioma-specific oncolytic immunotherapy enabled by immunopeptidomics of murine and human mesothelioma tumors.

Malignant pleural mesothelioma (MPM) is an aggressive tumor with a poor prognosis. As the available therapeutic options show a lack of efficacy, novel therapeutic strategies are urgently needed. Given its T-cell infiltration, we hypothesized that MPM is a suitable target for therapeutic cancer vaccination.

Personalizing Oncolytic Virotherapy.

The use of oncolytic viruses has become an attractive tool in the clinics for the treatment of various tumor types. Such viruses are genetically modified to conditionally replicate in malignant cells while unharming healthy cells. This platform offers a highly specific tumor killing with exceptional safety profiles.

Controlled release of enhanced cross-hybrid IgGA Fc PD-L1 inhibitors using oncolytic adenoviruses.

Immune checkpoint inhibitors have clinical success in prolonging the life of many cancer patients. However, only a minority of patients benefit from such therapy, calling for further improvements. Currently, most PD-L1 checkpoint inhibitors in the clinic do not elicit Fc effector mechanisms that would substantially increase their efficacy.

Development of a Syrian hamster anti-PD-L1 monoclonal antibody enables oncolytic adenoviral immunotherapy modelling in an immunocompetent virus replication permissive setting.

Introduction: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of cancer, but preclinical testing of hypotheses such as combination therapies has been complicated, in part due to species incompatibility issues. For example, one of few known permissive animal models for oncolytic adenoviruses is the Syrian hamster, for which an ICI, mainly an anti-PD-L1 monoclonal antibody (mAb) was not previously available. In this study, we developed an anti-Syrian hamster PD-L1 mAb to enable the evaluation of safety and efficacy, when combining anti-PD-L1 with an oncolytic adenovirus encoding tumour necrosis factor alpha (TNFα) and interleukin-2 (IL-2) (Ad5/3-E2F-D24-hTNFα-IRES-hIL-2 or TILT-123).

Cancer immunotherapies: A hope for the uncurable?

The use of cancer immunotherapies is not novel but has been used over the decades in the clinic. Only recently have we found the true potential of stimulating an anti-tumor response after the breakthrough of checkpoint inhibitors. Cancer immunotherapies have become the first line treatment for many malignancies at various stages.

Characterization of Expanded Gamma Delta T Cells from Atypical X-SCID Patient Reveals Preserved Function and IL2RG-Mediated Signaling.

Abnormally high γδ T cell numbers among individuals with atypical SCID have been reported but detailed immunophenotyping and functional characterization of these expanded γδ T cells are limited. We have previously reported atypical SCID phenotype caused by hypomorphic IL2RG (NM_000206.3) c.

A novel cancer vaccine for melanoma based on an approved vaccine against measles, mumps, and rubella.

Common vaccines for infectious diseases have been repurposed as cancer immunotherapies. The intratumoral administration of these repurposed vaccines can induce immune cell infiltration into the treated tumor. Here, we have used an approved trivalent live attenuated measles, mumps, and rubella (MMR) vaccine in our previously developed PeptiENV cancer vaccine platform.

Peptides-Coated Oncolytic Vaccines for Cancer Personalized Medicine.

Oncolytic Viruses (OVs) work through two main mechanisms of action: the direct lysis of the virus-infected cancer cells and the release of tumor antigens as a result of the viral burst. In this sc.enario, the OVs act as cancer vaccines, since the immunogenicity of the virus is combined with tumor antigens, that direct the specificity of the anti-tumor adaptive immune response.

A novel immunopeptidomic-based pipeline for the generation of personalized oncolytic cancer vaccines.

Besides the isolation and identification of major histocompatibility complex I-restricted peptides from the surface of cancer cells, one of the challenges is eliciting an effective antitumor CD8+ T-cell-mediated response as part of therapeutic cancer vaccine. Therefore, the establishment of a solid pipeline for the downstream selection of clinically relevant peptides and the subsequent creation of therapeutic cancer vaccines are of utmost importance. Indeed, the use of peptides for eliciting specific antitumor adaptive immunity is hindered by two main limitations: the efficient selection of the most optimal candidate peptides and the use of a highly immunogenic platform to combine with the peptides to induce effective tumor-specific adaptive immune responses.

PeptiCHIP: A Microfluidic Platform for Tumor Antigen Landscape Identification.

Identification of HLA class I ligands from the tumor surface (ligandome or immunopeptidome) is essential for designing T-cell mediated cancer therapeutic approaches. However, the sensitivity of the process for isolating MHC-I restricted tumor-specific peptides has been the major limiting factor for reliable tumor antigen characterization, making clear the need for technical improvement. Here, we describe our work from the fabrication and development of a microfluidic-based chip (PeptiCHIP) and its use to identify and characterize tumor-specific ligands on clinically relevant human samples.

Novel oncolytic adenovirus expressing enhanced cross-hybrid IgGA Fc PD-L1 inhibitor activates multiple immune effector populations leading to enhanced tumor killing in vitro, in vivo and with patient-derived tumor organoids.

Background: Despite the success of immune checkpoint inhibitors against PD-L1 in the clinic, only a fraction of patients benefit from such therapy. A theoretical strategy to increase efficacy would be to arm such antibodies with Fc-mediated effector mechanisms. However, these effector mechanisms are inhibited or reduced due to toxicity issues since PD-L1 is not confined to the tumor and also expressed on healthy cells.

Novel personalized cancer vaccine platform based on Bacillus Calmette-Guèrin.

Background: Intratumoral BCG therapy, one of the earliest immunotherapies, can lead to infiltration of immune cells into a treated tumor. However, an increase in the number of BCG-induced tumor-specific T cells in the tumor microenvironment could lead to enhanced therapeutic effects.

Methods: Here, we have developed a novel cancer vaccine platform based on BCG that can broaden BCG-induced immune responses to include tumor antigens.

Viral Molecular Mimicry Influences the Antitumor Immune Response in Murine and Human Melanoma.

Molecular mimicry is one of the leading mechanisms by which infectious agents can induce autoimmunity. Whether a similar mechanism triggers an antitumor immune response is unexplored, and the role of antiviral T cells infiltrating the tumor has remained anecdotal. To address these questions, we first developed a bioinformatic tool to identify tumor peptides with high similarity to viral epitopes.

GAMER-Ad: a novel and rapid method for generating recombinant adenoviruses.

Oncolytic adenoviruses have become ideal agents in the path toward treating cancer. Such viruses have been engineered to conditionally replicate in malignant cells in which certain signaling pathways have been disrupted. Other than such oncolytic properties, the viruses need to activate the immune system in order to sustain a long-term response.

Patient-Derived Organoids for Precision Cancer Immunotherapy.

Cancer immunotherapy has revolutionized the way tumors are treated. Nevertheless, efficient and robust testing platforms are still missing, including clinically relevant human tumor assays that allow pretreatment testing of cancer therapies and selection of the most efficient and safe therapy for a specific patient. In the case of immunotherapy, this testing platform would require not only cancer cells, but also the tumor microenvironment, including immune cells.

Novel chimerized IgA CD20 antibodies: Improving neutrophil activation against CD20-positive malignancies.

Current combination therapies elicit high response rates in B cell malignancies, often using CD20 antibodies as the backbone of therapy. However, many patients eventually relapse or develop progressive disease. Therefore, novel CD20 antibodies combining multiple effector mechanisms were generated.

Exploiting Preexisting Immunity to Enhance Oncolytic Cancer Immunotherapy.

Because of the high coverage of international vaccination programs, most people worldwide have been vaccinated against common pathogens, leading to acquired pathogen-specific immunity with a robust memory T-cell repertoire. Although CD8 antitumor cytotoxic T lymphocytes (CTL) are the preferred effectors of cancer immunotherapy, CD4 T-cell help is also required for an optimal antitumor immune response to occur. Hence, we investigated whether the pathogen-related CD4 T-cell memory populations could be reengaged to support the CTLs, converting a weak primary antitumor immune response into a stronger secondary one.

Artificially cloaked viral nanovaccine for cancer immunotherapy.

Virus-based cancer vaccines are nowadays considered an interesting approach in the field of cancer immunotherapy, despite the observation that the majority of the immune responses they elicit are against the virus and not against the tumor. In contrast, targeting tumor associated antigens is effective, however the identification of these antigens remains challenging. Here, we describe ExtraCRAd, a multi-vaccination strategy focused on an oncolytic virus artificially wrapped with tumor cancer membranes carrying tumor antigens.