Vaccines for HPV-associated diseases.

Human papillomavirus (HPV) infection represents a significant global health concern owing to its role in the etiology of conditions ranging from benign low-grade lesions to cancers of the cervix, head and neck, anus, vagina, vulva, and penis. Prophylactic vaccination programs, primarily targeting adolescent girls, have achieved dramatic reductions in rates of HPV infection and cervical cancer in recent years. However, there is a clear demand for a strategy to manage the needs of the many people who are already living with persistent HPV infection and/or HPV-associated conditions.

Interim Results of a Phase 1/2 Open-Label Study of INO-3107 for HPV-6 and/or HPV-11-Associated Recurrent Respiratory Papillomatosis.

Objective: To evaluate the safety, immunogenicity, and efficacy of INO-3107, a DNA immunotherapy designed to elicit targeted T-cell responses against human papillomavirus (HPV) types 6 and 11, in adult patients with recurrent respiratory papillomatosis (RRP; NCT04398433).

Methods: Eligible patients required ≥2 surgical interventions for RRP in the year preceding dosing. INO-3107 was administered by intramuscular (IM) injection followed by electroporation (EP) on weeks 0, 3, 6, and 9.

Phase I Trial of a Therapeutic DNA Vaccine for Preventing Hepatocellular Carcinoma from Chronic Hepatitis C Virus (HCV) Infection.

Unlabelled: Chronic hepatitis C can lead to cirrhosis and hepatocellular carcinoma. We studied the safety and immunogenicity of a novel therapeutic hepatitis C virus (HCV) genotype 1a/1b consensus DNA vaccine, INO-8000, encoding HCV NS3, NS4A, NS4B, and NS5A proteins alone or co-administered with DNA-encoding IL12 (INO-9012), a human cytokine that stimulates cellular immune function, in individuals with chronic hepatitis C. This was a phase I, multisite dose-escalation trial with an expansion cohort evaluating doses of 0, 0.

There's something about a pattern: Choice between pattern and random sequences in implicit learning.

Three experiments examined the preference for pattern versus random sequences. In all experiments the elements composing the sequences were visual images presented sequentially on a touchscreen. Reinforcement was randomly programmed on .

Gastric Histopathologic Findings Are Similar in Portal Hypertension Patients With and Without Endoscopic Portal Hypertensive Gastropathy.

Objectives: Portal hypertensive gastropathy (PHG) is a diagnosis made based on endoscopic findings in the appropriate clinical setting. Biopsy may be taken during endoscopy for correlation, but the pathologist may encounter a myriad of nonspecific histologic findings. We undertook this study to evaluate contexts where a histologic diagnosis of PHG might be rendered on biopsy.

Neoadjuvant Yttrium-90 Transarterial Radioembolization with Resin Microspheres Prescribed Using the Medical Internal Radiation Dose Model for Intrahepatic Cholangiocarcinoma.

Purpose: To evaluate outcomes of patients with intrahepatic cholangiocarcinoma (iCCA) undergoing neoadjuvant yttrium-90 (Y) transarterial radioembolization (TARE) with resin microspheres prescribed using the Medical Internal Radiation Dose (MIRD) model.

Materials And Methods: This retrospective institutional review board-approved study included 37 patients with iCCA treated with Y-TARE from October 2015 to September 2020. The primary outcome was overall survival (OS) from Y-TARE.

Phase 1 study of safety, tolerability and immunogenicity of the human telomerase (hTERT)-encoded DNA plasmids INO-1400 and INO-1401 with or without IL-12 DNA plasmid INO-9012 in adult patients with solid tumors.

Background: Human telomerase reverse transcriptase (hTERT) is frequently classified as a 'universal' tumor associated antigen due to its expression in a vast number of cancers. We evaluated plasmid DNA-encoded hTERT as an immunotherapy across nine cancer types.

Methods: A phase 1 clinical trial was conducted in adult patients with no evidence of disease following definitive surgery and standard therapy, who were at high risk of relapse.

Durability of response to VGX-3100 treatment of HPV16/18 positive cervical HSIL.

VGX-3100 is an investigational DNA-based immunotherapy being developed as an alternative to surgery and ablation for cervical High-Grade Squamous Intraepithelial Lesion (HSIL) with the aim of preserving reproductive health while treating precancerous disease. Response durability up to 1.5 y following dosing is now reported.

Proximity-dependent Proteomics Reveals Extensive Interactions of Protocadherin-19 with Regulators of Rho GTPases and the Microtubule Cytoskeleton.

Protocadherin-19 belongs to the cadherin family of cell surface receptors and has been shown to play essential roles in the development of the vertebrate nervous system. Mutations in human Protocadherin-19 (PCDH19) lead to PCDH19 Female-limited epilepsy (PCDH19 FLE) in humans, characterized by the early onset of epileptic seizures in children and a range of cognitive and behavioral problems in adults. Despite being considered the second most prevalent gene in epilepsy, very little is known about the intercellular pathways in which it participates.

Robust antibody and cellular responses induced by DNA-only vaccination for HIV.

BACKGROUNDHVTN 098, a randomized, double-blind, placebo-controlled trial, evaluated the safety, tolerability, and immunogenicity of PENNVAX-GP HIV DNA vaccine, administered with or without plasmid IL-12 (pIL-12), via intradermal (ID) or intramuscular (IM) electroporation (EP) in healthy, HIV-uninfected adults. The study tested whether PENNVAX-GP delivered via ID/EP at one-fifth the dose could elicit equivalent immune responses to delivery via IM/EP and whether inclusion of pIL-12 provided additional benefit.METHODSParticipants received DNA encoding HIV-1 env/gag/pol in 3 groups: 1.

Brain Abscess as Severe Presentation of Specific Granule Deficiency.

Severe invasive infections such as brain abscess in a child should prompt an immune evaluation. Specific granule deficiency (SGD) is a rare morphologic neutrophil granular defect characterized by reduced granules within neutrophils, absence of granule proteins, and bilobed nuclei. Patients are susceptible to invasive bacterial infections and infections.

Using Adalimumab to Treat Autoimmune Enteropathy.

Autoimmune enteropathy is a rare condition seen in adults with limited therapeutic options available. It manifests with profuse diarrhea and malnourishment. The diagnosis is made through a combination of clinical, serologic, and histologic parameters.

CD8 T Cells Impact Rising PSA in Biochemically Relapsed Cancer Patients Using Immunotherapy Targeting Tumor-Associated Antigens.

The management of men with prostate cancer (PCa) with biochemical recurrence following local definitive therapy remains controversial. Early use of androgen deprivation therapy (ADT) leads to significant side effects. Developing an alternative, clinically effective, and well-tolerated therapy remains an unmet clinical need.

A Phase 1 Trial Assessing the Safety and Tolerability of a Therapeutic DNA Vaccination Against HPV16 and HPV18 E6/E7 Oncogenes After Chemoradiation for Cervical Cancer.

Purpose: This study assessed the safety and tolerability of therapeutic immunization against the human papillomavirus (HPV) viral oncoproteins E6 and E7 in patients with cervical cancer after chemoradiation.

Methods And Materials: MEDI0457 (INO-3112) is a DNA-based vaccine targeting E6 and E7 of HPV-16/18 that is coinjected with an IL-12 plasmid followed by electroporation with the CELLECTRA 5P device. At 2 to 4 weeks after chemoradiation, patients with newly diagnosed stage IB1-IVA (cohort 1) or persistent/recurrent (cohort 2) cervical cancers were treated with 4 immunizations of MEDI0457 every 4 weeks.

Immune Therapy Targeting E6/E7 Oncogenes of Human Paillomavirus Type 6 (HPV-6) Reduces or Eliminates the Need for Surgical Intervention in the Treatment of HPV-6 Associated Recurrent Respiratory Papillomatosis.

Unlabelled: Background: Recurrent respiratory papillomatosis (RRP) is a rare disorder characterized by the generation of papillomas of the aerodigestive tract, usually associated with human papilloma virus (HPV) subtypes 6, 11. INO-3106 is a DNA plasmid-based immunotherapy targeting E6 and E7 proteins of HPV6, in order to create a robust immune T cell response.

Methods: Testing of INO-3016 in animal models confirmed immunogenicity of the DNA-based therapy.

Safety and immunogenicity of VGX-3100 formulations in a healthy young adult population.

HPV remains the most common sexually transmitted disease worldwide, despite improvements in awareness, screening, prophylactic vaccination uptake, and surgical treatment. VGX-3100 is an immunotherapy that uses electroporation to introduce DNA encoding for modified HPV-16 and HPV-18, E6-and E7 proteins into myocytes to stimulate an effector T cell response. We now report immunogenicity and safety of VGX-3100 for a refrigeration-stable formulation, which improves patient-care setting usability.

Budd-Chiari Syndrome in a Patient With Simultaneous Diagnosis of Hepatic Sarcoidosis and Nodular Regenerative Hyperplasia.

Budd-Chiari syndrome (BCS) is a rare vascular disorder characterized by an obstruction of the hepatic venous outflow. Nodular regenerative hyperplasia (NRH) may develop as a result of an underlying autoimmune disease such as hepatic sarcoidosis. Only a few case reports have described cases with either NRH or hepatic sarcoidosis associated with BCS.

Congenital Epidermoid Cyst of the Liver: A Rare Entity Characterized by Antenatal Onset, Slow Postnatal Growth, and Consistent Histologic and Immunohistologic Features.

Background: There are only 15 reported hepatic epidermoid cysts; they include patients presenting congenitally through adulthood, with varied speculations about pathogenesis. Aside from recently reported pancytokeratin staining, no other descriptions have included immunohistochemistry. Splenic epidermoid cysts were recently characterized as positive for HBME-1, p63, CEA, CK7 (luminal), and CK19.

Intradermal SynCon® Ebola GP DNA Vaccine Is Temperature Stable and Safely Demonstrates Cellular and Humoral Immunogenicity Advantages in Healthy Volunteers.

Background: Nonlive vaccine approaches that are simple to deliver and stable at room temperature or 2-8°C could be advantageous in controlling future Ebola virus (EBOV) outbreaks. Using an immunopotent DNA vaccine that generates protection from lethal EBOV challenge in small animals and nonhuman primates, we performed a clinical study to evaluate both intramuscular (IM) and novel intradermal (ID) DNA delivery.

Methods: Two DNA vaccine candidates (INO-4201 and INO-4202) targeting the EBOV glycoprotein (GP) were evaluated for safety, tolerability, and immunogenicity in a phase 1 clinical trial.

Immunotherapy Targeting HPV16/18 Generates Potent Immune Responses in HPV-Associated Head and Neck Cancer.

Purpose: Clinical responses with programmed death (PD-1) receptor-directed antibodies occur in about 20% of patients with advanced head and neck squamous cell cancer (HNSCCa). Viral neoantigens, such as the E6/E7 proteins of HPV16/18, are attractive targets for therapeutic immunization and offer an immune activation strategy that may be complementary to PD-1 inhibition.

Patients And Methods: We report phase Ib/II safety, tolerability, and immunogenicity results of immunotherapy with MEDI0457 (DNA immunotherapy targeting HPV16/18 E6/E7 with IL12 encoding plasmids) delivered by electroporation with CELLECTRA constant current device.

A swap methodology applied to implicit sequence learning.

Two experiments used a methodology in which elements in a serially presented sequence of 5 elements were randomly reinforced during training. To assess what was learned, elements were systematically swapped with each other during testing. The usual outcome measures in implicit sequence learning of this type are either a random test in which elements are disarrayed, or pairwise tests in which subjects choose between two elements.

Reversible Control of Network Properties in Azobenzene-Containing Hyaluronic Acid-Based Hydrogels.

Biomimetic hydrogels fabricated from biologically derived polymers, such as hyaluronic acid (HA), are useful for numerous biomedical applications. Due to the dynamic nature of biological processes, it is of great interest to synthesize hydrogels with dynamically tunable network properties where various functions (e.g.