In situ vaccination via tissue-targeted cDC1 expansion enhances the immunogenicity of chemoradiation and immunotherapy.

Even with the prolific clinical use of next-generation cancer therapeutics, many tumors remain unresponsive or become refractory to therapy, creating a medical need. In cancer, DCs are indispensable for T cell activation, so there is a restriction on cytotoxic T cell immunity if DCs are not present in sufficient numbers in the tumor and draining lymph nodes to take up and present relevant cancer antigens. To address this bottleneck, we developed a therapeutic based on albumin fused with FMS-related tyrosine kinase 3 ligand (Alb-Flt3L) that demonstrated superior pharmacokinetic properties compared with Flt3L, including significantly longer half-life, accumulation in tumors and lymph nodes, and cross-presenting-DC expansion following a single injection.

The effectiveness of an unsupervised home-based pulmonary rehabilitation with self-management program in patients with chronic obstructive pulmonary disease.

Aims: To assess the effectiveness of an unsupervised home-based pulmonary rehabilitation with self-management program in patients with chronic obstructive pulmonary disease (COPD).

Background: A few recent studies have shown that unsupervised home-based pulmonary rehabilitation can improve the clinical outcome of patients with COPD. More studies are needed to prove its benefits.

Localization of Salmonella and albumin-IL-2 to the tumor microenvironment augments anticancer T cell immunity.

Background: For centuries, microbial-based agents have been investigated as a therapeutic modality for the treatment of cancer. In theory, these methods would be cheap to produce, broadly applicable in a wide array of cancer types, and could synergize with other cancer treatment strategies. We aimed to assess the efficacy of combining microbial-based therapy using Salmonella SL7207 with interleukin-2 (IL-2), a potent immunostimulatory agent, in the treatment of murine colon carcinoma.

Delivery of IL-2 to the T Cell Surface Through Phosphatidylserine Permits Robust Expansion of CD8 T Cells.

The phospholipid phosphatidylserine (PS) is naturally maintained on the cytoplasmic side of the plasma membrane. Independent of apoptosis, PS is redistributed to the surface of CD8 T cells in response to TCR-mediated activation. Annexin V (AnnV) is a protein known to bind PS with high affinity and has been effectively utilized to anchor antigen to the surface of CD8 T cells.

In vivo characterization of emerging SARS-CoV-2 variant infectivity and human antibody escape potential.

As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spreads, variants with enhanced virulence and transmissibility have emerged. Although in vitro systems allow rapid characterization, they do not fully recapitulate the dynamic interaction of virions and neutralizing antibodies in the airway. Here, we demonstrate that the N501Y variant permits respiratory infection in unmodified mice.

A novel pseudovirus-based mouse model of SARS-CoV-2 infection to test COVID-19 interventions.

Background: The spread of SARS-CoV-2, the virus that causes Coronavirus Disease 2019 (COVID-19), has been characterized as a worldwide pandemic. Currently, there are few preclinical animal models that suitably represent infection, as the main point of entry to human cells is via human angiotensin-converting enzyme 2 (ACE2) which is not present in typical preclinical mouse strains. Additionally, SARS-CoV-2 is highly virulent and unsafe for use in many research facilities.

Lineage-Specific Alterations in Gynecologic Neoplasms with Choriocarcinomatous Differentiation: Implications for Origin and Therapeutics.

Purpose: Choriocarcinoma is most commonly gestational (androgenetic or biparental) but can be of germ cell origin or can develop as a component of a somatic neoplasm (genetically related to the patient). The latter type are aggressive neoplasms for which the underlying genetic alterations are not well characterized.

Experimental Design: To investigate the relationship between the different components of somatic neoplasms with choriocarcinomatous elements, the genetic differences between gestational and nongestational tumors, and identify potential targetable alterations, we analyzed 23 samples from 11 tumors, including five gynecologic-type somatic neoplasms with choriocarcinomatous differentiation (two to three different components each) and six pure choriocarcinomas, for somatic mutations, single-nucleotide polymorphisms, and PD-L1 expression.

A review of clinical trials of biologic agents and small molecules for psoriasis in Asian subjects.

Introduction: Biologics are increasingly used in the treatment of moderate to severe psoriasis. However, most of the pivotal studies were performed mainly in western countries. The purpose of this review article was to compare the differences of clinical trial results between Asian and Western subjects of psoriasis regarding baseline demographics, efficacy, dermatology life quality index, safety and antidrug antibodies.

Creation of a Merkel cell polyomavirus small T antigen-expressing murine tumor model and a DNA vaccine targeting small T antigen.

Background: Merkel cell polyomavirus (MCPyV) is a DNA virus expressing transcripts similar to the large T (LT) and small T (ST) transcripts of SV40, which has been implicated in the pathogenesis of Merkel cell carcinoma (MCC), a rare and highly aggressive neuroendocrine skin cancer. MCPyV LT antigen expression was found to be a requirement for MCC tumor maintenance and ST protein also likely contributes to the carcinogenesis of MCC. Previously, we have identified the probable immunodominant epitope of MCPyV LT and developed a DNA vaccine encoding this epitope linked to calreticulin.