High-resolution epitope mapping and characterization of SARS-CoV-2 antibodies in large cohorts of subjects with COVID-19.

As Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) continues to spread, characterization of its antibody epitopes, emerging strains, related coronaviruses, and even the human proteome in naturally infected patients can guide the development of effective vaccines and therapies. Since traditional epitope identification tools are dependent upon pre-defined peptide sequences, they are not readily adaptable to diverse viral proteomes. The Serum Epitope Repertoire Analysis (SERA) platform leverages a high diversity random bacterial display library to identify proteome-independent epitope binding specificities which are then analyzed in the context of organisms of interest.

Immunogenic amino acid motifs and linear epitopes of COVID-19 mRNA vaccines.

Reverse vaccinology is an evolving approach for improving vaccine effectiveness and minimizing adverse responses by limiting immunizations to critical epitopes. Towards this goal, we sought to identify immunogenic amino acid motifs and linear epitopes of the SARS-CoV-2 spike protein that elicit IgG in COVID-19 mRNA vaccine recipients. Paired pre/post vaccination samples from N = 20 healthy adults, and post-vaccine samples from an additional N = 13 individuals were used to immunoprecipitate IgG targets expressed by a bacterial display random peptide library, and preferentially recognized peptides were mapped to the spike primary sequence.

Phase Ib study of patients with metastatic castrate-resistant prostate cancer treated with different sequencing regimens of atezolizumab and sipuleucel-T.

Background: Combining an immune checkpoint inhibitor with a tumor vaccine may modulate the immune system to leverage complementary mechanisms of action that lead to sustained T-cell activation and a potent prolonged immunotherapeutic response in metastatic castration resistant prostate cancer (mCRPC).

Methods: Subjects with asymptomatic or minimally symptomatic mCRPC were randomly assigned in a 1:1 ratio to receive either atezolizumab followed by sipuleucel-T (Arm 1) or sipuleucel-T followed by atezolizumab (Arm 2). The primary endpoint was safety, while secondary endpoints included preliminary clinical activity such as objective tumor response and systemic immune responses that could identify key molecular and immunological changes associated with sequential administration of atezolizumab and sipuleucel-T.

Protein-Based Immunome Wide Association Studies (PIWAS) for the Discovery of Significant Disease-Associated Antigens.

Identification of the antigens associated with antibodies is vital to understanding immune responses in the context of infection, autoimmunity, and cancer. Discovering antigens at a proteome scale could enable broader identification of antigens that are responsible for generating an immune response or driving a disease state. Although targeted tests for known antigens can be straightforward, discovering antigens at a proteome scale using protein and peptide arrays is time consuming and expensive.

Autoantibody Landscape in Patients with Advanced Prostate Cancer.

Purpose: Autoantibody responses in cancer are of great interest, as they may be concordant with T-cell responses to cancer antigens or predictive of response to cancer immunotherapies. Thus, we sought to characterize the antibody landscape of metastatic castration-resistant prostate cancer (mCRPC).

Experimental Design: Serum antibody epitope repertoire analysis (SERA) was performed on patient serum to identify tumor-specific neoepitopes.

Fast quantitative optical detection of heat dissipation by surface plasmon polaritons.

Heat management at the nanoscale is an issue of increasing importance. In optoelectronic devices the transport and decay of plasmons contribute to the dissipation of heat. By comparison of experimental data and simulations we demonstrate that it is possible to gain quantitative information about excitation, propagation and decay of surface plasmon polaritons (SPPs) in a thin gold stripe supported by a silicon membrane.

Ablation of B7-H3 but Not B7-H4 Results in Highly Increased Tumor Burden in a Murine Model of Spontaneous Prostate Cancer.

The costimulatory molecules B7-H3 and B7-H4 are overexpressed in a variety of human tumors and have been hypothesized as possible biomarkers and immunotherapeutic targets. Despite this potential, the predominating uncertainty about their functional implication in tumor-host interaction hampers their evaluation as a target for cancer therapy. By means of a highly physiologic, spontaneous tumor model in mice, we establish a causal link between B7-H3 and host tumor control and found B7-H4 to be redundant.

Lateral and temporal dependence of the transport through an atomic gold contact under light irradiation: signature of propagating surface plasmon polaritons.

Metallic point contacts (MPCs) with dimensions comparable to the Fermi wavelength of conduction electrons act as electronic waveguides and might operate as plasmon transmitters. Here we present a correlated study of optical and conductance response of MPCs under irradiation with laser light. For elucidating the role of surface plasmon polaritons (SPPs), we integrate line gratings into the leads that increase the SPP excitation efficiency.

CTLA-4 blockade synergizes with cryoablation to mediate tumor rejection.

We report that cryoablation of primary tumors synergizes with anti-CTLA-4 treatment to mediate rejection of secondary tumors in the TRAMP mouse model of prostate cancer. T cells, in particular CD8(+) T cells specific for the TRAMP antigen SPAS-1, were enriched in both secondary tumors and spleens of combination-treated mice.

Augmented IL-15Rα expression by CD40 activation is critical in synergistic CD8 T cell-mediated antitumor activity of anti-CD40 antibody with IL-15 in TRAMP-C2 tumors in mice.

IL-15 has potential as an immunotherapeutic agent for cancer treatment because it is a critical factor for the proliferation and activation of NK and CD8(+) T cells. However, monotherapy of patients with malignancy with IL-15 that has been initiated may not be optimal, because of the limited expression of the private receptor, IL-15Rα. We demonstrated greater CD8 T cell-mediated therapeutic efficacy using a combination regimen of murine IL-15 administered with an agonistic anti-CD40 Ab (FGK4.

Simultaneous inhibition of two regulatory T-cell subsets enhanced Interleukin-15 efficacy in a prostate tumor model.

IL-15 has potential as an immunotherapeutic agent for cancer treatment because of its ability to effectively stimulate CD8 T cell, natural killer T cell, and natural killer cell immunity. However, its effectiveness may be limited by negative immunological checkpoints that attenuate immune responses. Recently a clinical trial of IL-15 in cancer immunotherapy was initiated.

Potent induction of tumor immunity by combining tumor cryoablation with anti-CTLA-4 therapy.

Thermal ablation to destroy tumor tissue may help activate tumor-specific T cells by elevating the presentation of tumor antigens to the immune system. However, the antitumor activity of these T cells may be restrained by their expression of the inhibitory T-cell coreceptor CTLA-4, the target of the recently U.S.

Subharmonic resonant optical excitation of confined acoustic modes in a free-standing semiconductor membrane at GHz frequencies with a high-repetition-rate femtosecond laser.

We propose subharmonic resonant optical excitation with femtosecond lasers as a new method for the characterization of phononic and nanomechanical systems in the gigahertz to terahertz frequency range. This method is applied for the investigation of confined acoustic modes in a free-standing semiconductor membrane. By tuning the repetition rate of a femtosecond laser through a subharmonic of a mechanical resonance we amplify the mechanical amplitude, directly measure the linewidth with megahertz resolution, infer the lifetime of the coherently excited vibrational states, accurately determine the system's quality factor, and determine the amplitude of the mechanical motion with femtometer resolution.

Tumor associated endothelial expression of B7-H3 predicts survival in ovarian carcinomas.

B7-H3 and B7x are members of the B7 family of immune regulatory ligands that are thought to attenuate peripheral immune responses through co-inhibition. Previous studies have correlated their overexpression with poor prognosis and decreased tumor-infiltrating lymphocytes in various carcinomas including uterine endometrioid carcinomas, and mounting evidence supports an immuno-inhibitory role in ovarian cancer prognosis. We sought to examine the expression of B7-H3 and B7x in 103 ovarian borderline tumors and carcinomas and study associations with clinical outcome.

Optical transmission and laser structuring of silicon membranes.

The optical linear and nonlinear properties of ~ 340-nm thick Si membranes were investigated. The investigation included both experiments in which the reflection and transmission from the membranes were measured, and finite differences time domain simulations. The linear optical transmission of the Si membranes can be controlled by changing the thickness of a thermally grown oxide on the membrane.

Can local radiofrequency ablation of tumors generate systemic immunity against metastatic disease?

Radiofrequency (RF) ablation may have the potential to turn a patient's tumor into an endogenous tumor vaccine; in this context of RF ablation-triggered immune system stimulation, the report by Dromi et al demonstrates a systemic immune response after local RF ablation in a mouse model.

Nanofabricated adjustable multicontact devices on membranes.

Adjustable atomic size contacts realized by break junctions have become a standard tool during the last decade. Although nanofabricated break junctions may in principle be incorporated onto complex electronic circuits, a fundamental drawback of the standard break junction technique is its limitation to a single adjustable junction per device. We have fabricated single break junctions as well as devices containing two break junctions on a silicon membrane.

SPAS-1 (stimulator of prostatic adenocarcinoma-specific T cells)/SH3GLB2: A prostate tumor antigen identified by CTLA-4 blockade.

Discovery of immunologically relevant antigens in prostate cancer forms the basis for developing more potent active immunotherapy. We report here a strategy using the transgenic adenocarcinoma of mouse prostate (TRAMP) model, which allows for the functional identification of immunogenic prostate tumor antigens with relevance for human immunotherapy. Using a combination of active tumor vaccination in the presence of CTL-associated antigen 4 (CTLA-4) in vivo blockade, we elicited tumor-specific T cells used to expression clone the first T cell-defined TRAMP tumor antigen, called Spas-1 (stimulator of prostatic adenocarcinoma specific T cells-1).

Inducible costimulator is required for type 2 antibody isotype switching but not T helper cell type 2 responses in chronic nematode infection.

Inducible costimulator (ICOS) has been suggested to perform an important role in T helper cell type 2 (Th2) responses, germinal center formation, and isotype switching. The role of ICOS in chronic Th2 responses was studied in a nematode model with the filarial parasite, Brugia malayi. Contrary to expectations, we did not observe a significant defect in IL-4-producing Th2 cells in ICOS-/- mice or in eosinophil recruitment.

B7x: a widely expressed B7 family member that inhibits T cell activation.

B7 family proteins provide costimulatory signals that regulate T cell responses. Here we report the third set of B7 family-related T cell inhibitory molecules with the identification of a homolog of the B7 family, B7x. It is expressed in immune cells, nonlymphoid tissues, and some tumor cell lines.

[Myelosclerosis : pseudo-tumors forms (author's transl)].

Signs of pseudo-tumor growth may be seen in myelosclerosis. Eight personal cases and a review of the literature are discussed in this article. The observations here reported cover pseudo-tumors occurring in ganglia, liver, suprarenals (3), abdomen and pancreas.

[Comparative study of A, B, and H substances in stromas with and without lipid removal. Studies of the erythrocyte membrane].

Human erythrocyte membranes were prepared by hypotonic hemolysis and extracted with water pH 7, EDTA and mercapto-ethanol solutions pH 8. The complex residue which contains lipids, proteins and the A, B, H antigens was dissolved in SDS and analysed by preparative acrylamide gel electrophoresis in the presence of SDS. Each fraction was assayed for A, B or H blood-group activity by hemagglutination inhibition tests.