Association of Tumor Mutational Burden and Immune Gene Expression with Response to PD-1 Blockade by Sasanlimab Across Tumor Types and Routes of Administration.

Background: Sasanlimab is a monoclonal antibody that binds to the programmed cell death receptor 1 (PD-1). Anti-PD-1 monoclonal antibodies have improved patient clinical outcomes; however, not all treated patients derive clinical benefit. Further insights on potential biomarkers beyond PD-L1 expression levels would help to identify the patients most likely to respond to treatment.

A Phase I, Open-Label, Dose-Escalation Study of the OX40 Agonist Ivuxolimab in Patients with Locally Advanced or Metastatic Cancers.

Purpose: Stimulation of effector T cells is an appealing immunotherapeutic approach in oncology. OX40 (CD134) is a costimulatory receptor expressed on activated CD4 and CD8 T cells. Induction of OX40 following antigen recognition results in enhanced T-cell activation, proliferation, and survival, and OX40 targeting shows therapeutic efficacy in preclinical studies.

Reconfigurable all-dielectric metalens with diffraction-limited performance.

Active metasurfaces, whose optical properties can be modulated post-fabrication, have emerged as an intensively explored field in recent years. The efforts to date, however, still face major performance limitations in tuning range, optical quality, and efficiency, especially for non-mechanical actuation mechanisms. In this paper, we introduce an active metasurface platform combining phase tuning in the full 2π range and diffraction-limited performance using an all-dielectric, low-loss architecture based on optical phase change materials (O-PCMs).

Addressing resistance to immune checkpoint inhibitor therapy: an urgent unmet need.

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of various cancers by reversing the immunosuppressive mechanisms employed by tumors to restore anticancer immunity. Although ICIs have demonstrated substantial clinical efficacy, patient response can vary in depth and duration, and many do not respond at all or eventually develop resistance. ICI resistance mechanisms can be tumor-intrinsic, related to the tumor microenvironment or patient-specific factors.

Ovarian cancer: new strategies and emerging targets for the treatment of patients with advanced disease.

Recently approved therapies have contributed to a significant progress in the management of ovarian cancer; yet, more options are needed to further improve outcomes in patients with advanced disease. Here we review the rationale and ongoing clinical trials of novel combination strategies involving chemotherapy, poly ADP ribose polymerase, programmed death 1 (PD-1)/PD-ligand 1 immune checkpoint and/or vascular endothelial growth factor receptor inhibitors. Further, we discuss novel agents aimed at targets associated with ovarian cancer growth or progression that are emerging as potential new treatment approaches.

Airway profile of bioactive lipids predicts early progression of lung disease in cystic fibrosis.

Background: Previously, we showed that abnormal levels of bioactive lipids in bronchoalveolar lavage fluid (BALF) from infants with cystic fibrosis (CF) correlated with early structural lung damage.

Method: To extend these studies, BALF bioactive lipid measurement by mass spectrometry and chest computed tomography (CT, combined with the sensitive PRAGMA-CF scoring method) were performed longitudinally at 2-year intervals in a new cohort of CF children (n = 21, aged 1-5 yrs).

Results: PRAGMA-CF, neutrophil elastase activity, and myeloperoxidase correlated with BALF lysolipids and isoprostanes, markers of oxidative stress, as well as prostaglandin E2 and combined ceramide precursors (Spearman's Rho > 0.

Analog Coupled Oscillator Based Weighted Ising Machine.

We report on an analog computing system with coupled non-linear oscillators which is capable of solving complex combinatorial optimization problems using the weighted Ising model. The circuit is composed of a fully-connected 4-node LC oscillator network with low-cost electronic components and compatible with traditional integrated circuit technologies. We present the theoretical modeling, experimental characterization, and statistical analysis our system, demonstrating single-run ground state accuracies of 98% on randomized MAX-CUT problem sets with binary weights and 84% with 5-bit weight resolutions.

Broadband transparent optical phase change materials for high-performance nonvolatile photonics.

Optical phase change materials (O-PCMs), a unique group of materials featuring exceptional optical property contrast upon a solid-state phase transition, have found widespread adoption in photonic applications such as switches, routers and reconfigurable meta-optics. Current O-PCMs, such as Ge-Sb-Te (GST), exhibit large contrast of both refractive index (Δn) and optical loss (Δk), simultaneously. The coupling of both optical properties fundamentally limits the performance of many applications.

Humanistic and economic impact of subcutaneous versus intravenous administration of oncology biologics.

More oncology biologics are becoming available for subcutaneous (sc.) administration and are expected to provide useful therapeutic options. We evaluated evidence published in the past 5 years to assess the humanistic and economic impact of sc.

Assessment of Subcutaneous vs Intravenous Administration of Anti-PD-1 Antibody PF-06801591 in Patients With Advanced Solid Tumors: A Phase 1 Dose-Escalation Trial.

Importance: We assessed feasibility of monthly subcutaneous administration of PF-06801591, a humanized immunoglobulin G4 monoclonal antibody that binds to the programmed cell death (PD-1) receptor and blocks its interaction with PD-1 ligands.

Objective: To evaluate the safety, efficacy, and pharmacokinetics of PF-06801591 administered intravenously vs subcutaneously.

Design, Setting, And Participants: Ongoing phase 1, open-label, multicenter, dose-escalation study of 40 patients, 18 years or older, with locally advanced or metastatic solid tumors, enrolled between March 8, 2016, and March 5, 2018, from 4 US medical centers.

Immunogenicity of immunomodulatory, antibody-based, oncology therapeutics.

The increasing use of multiple immunomodulatory (IMD) agents for cancer therapies (e.g. antibodies targeting immune checkpoints, bispecific antibodies, and chimeric antigen receptor [CAR]-T cells), is raising questions on their potential immunogenicity and effects on treatment.

BMI Is a Better Body Proportionality Measure than the Ponderal Index and Weight-for-Length for Preterm Infants.

Background: Clinicians have observed preterm infants in the neonatal intensive care unit growing disproportionally; however, the only growth charts that have been available were from preterm infants born in the 1950s which utilized the ponderal index. Prior to creating the recently published BMI curves, we found only 1 reference justifying the use of the ponderal index.

Objectives: To determine the best measure of body proportionality for assessing growth in US preterm infants.

Effect of anisotropic electron momentum distribution of surface plasmon on internal photoemission of a Schottky hot carrier device.

We recently reported that an Au/TiO photonic crystal device for photochemical energy conversion showed a sub-bandgap photoresponse centered at the surface plasmon polariton (SPP) resonant wavelength of this device. Here we developed a theoretical modeling of the internal photoemission in this device by incorporating the effects of anisotropic hot electron momentum distribution caused by SPP. The influences of interband and intraband transition, anisotropic momentum distribution of hot electrons by SPP are integrated to model the internal quantum efficiency (IQE) of this device.

Tracking the Fate and Origin of Clinically Relevant Adoptively Transferred CD8 T Cells .

Adoptively transferred tumor-specific cells can mediate tumor regression in cancers refractory to conventional therapy. Autologous polyclonal tumor-specific cytotoxic T cells (CTL) generated from peripheral blood and infused into patients with metastatic melanoma show enhanced persistence, compared to equivalent numbers of more extensively expanded monoclonal CTL, and are associated with complete remissions (CR) in select patients. We applied high-throughput T cell receptor Vβ sequencing (HTTCS) to identify individual clonotypes within CTL products, track them post-infusion and then deduce the pre-adoptive transfer (endogenous) frequencies of cells ultimately responsible for tumor regression.

Electrically switchable diffractive waveplates with metasurface aligned liquid crystals.

Diffractive waveplates and equivalent metasurfaces provide a promising path for applications in thin film beam steering, tunable lenses, and polarization filters. However, fixed metasurfaces alone are unable to be tuned electronically. By combining metasurfaces with tunable liquid crystals, we experimentally demonstrate a single layer device capable of electrically switching a diffractive waveplate design at a measured peak diffraction efficiency of 35%, and a minimum switching voltage of 10V.

Surface plasmon assisted hot electron collection in wafer-scale metallic-semiconductor photonic crystals.

Plasmon assisted photoelectric hot electron collection in a metal-semiconductor junction can allow for sub-bandgap optical to electrical energy conversion. Here we report hot electron collection by wafer-scale Au/TiO metallic-semiconductor photonic crystals (MSPhC), with a broadband photoresponse below the bandgap of TiO. Multiple absorption modes supported by the 2D nano-cavity structure of the MSPhC extend the photon-metal interaction time and fulfill a broadband light absorption.

Melanoma and immunotherapy bridge 2015 : Naples, Italy. 1-5 December 2015.

MELANOMA BRIDGE 2015 KEYNOTE SPEAKER PRESENTATIONS Molecular and immuno-advances K1 Immunologic and metabolic consequences of PI3K/AKT/mTOR activation in melanoma Vashisht G. Y. Nanda, Weiyi Peng, Patrick Hwu, Michael A.

Talimogene Laherparepvec in Combination With Ipilimumab in Previously Untreated, Unresectable Stage IIIB-IV Melanoma.

Purpose: Combining immunotherapeutic agents with different mechanisms of action may enhance efficacy. We describe the safety and efficacy of talimogene laherparepvec (T-VEC; an oncolytic virus) in combination with ipilimumab (a cytotoxic T-lymphocyte-associated antigen 4 checkpoint inhibitor) in patients with advanced melanoma.

Methods: In this open-label, multicenter, phase Ib trial of T-VEC in combination with ipilimumab, T-VEC was administered intratumorally in week 1 (10(6) plaque-forming units/mL), then in week 4 and every 2 weeks thereafter (10(8) plaque-forming units/mL).

Origin and evolution of the T cell repertoire after posttransplantation cyclophosphamide.

Posttransplantation cyclophosphamide (PTCy) effectively prevents graft-versus-host disease (GVHD), but its immunologic impact is poorly understood. We assessed lymphocyte reconstitution via flow cytometry ( = 74) and antigen receptor sequencing ( = 35) in recipients of myeloablative, HLA-matched allogeneic BM transplantation using PTCy. Recovering T cells were primarily phenotypically effector memory with lower T cell receptor β () repertoire diversity than input donor repertoires.

Extremely Elastic Wearable Carbon Nanotube Fiber Strain Sensor for Monitoring of Human Motion.

The increasing demand for wearable electronic devices has made the development of highly elastic strain sensors that can monitor various physical parameters an essential factor for realizing next generation electronics. Here, we report an ultrahigh stretchable and wearable device fabricated from dry-spun carbon nanotube (CNT) fibers. Stretching the highly oriented CNT fibers grown on a flexible substrate (Ecoflex) induces a constant decrease in the conductive pathways and contact areas between nanotubes depending on the stretching distance; this enables CNT fibers to behave as highly sensitive strain sensors.

Direct Insulation-to-Conduction Transformation of Adhesive Catecholamine for Simultaneous Increases of Electrical Conductivity and Mechanical Strength of CNT Fibers.

Increase in conductivity and mechanical properties of a carbon nanotube (CNT) fiber inspired by mussel-adhesion chemistry is described. Infiltration of polydopamine into an as-drawn CNT fiber followed by pyrolysis results in a direct insulation-to-conduction transformation of poly(dopamine) into pyrolyzed-poly(dopamine) (py-PDA), retaining the intrinsic adhesive function of catecholamine. The py-PDA enhances both the electrical conductivity and the mechanical strength of the CNT fibers.

Global optimization of omnidirectional wavelength selective emitters/absorbers based on dielectric-filled anti-reflection coated two-dimensional metallic photonic crystals.

We report the design of dielectric-filled anti-reflection coated (ARC) two-dimensional (2D) metallic photonic crystals (MPhCs) capable of omnidirectional, polarization insensitive, wavelength selective emission/absorption. Using non-linear global optimization methods, optimized hafnium oxide (HfO2)-filled ARC 2D Tantalum (Ta) PhC designs exhibiting up to 26% improvement in emittance/absorptance at wavelengths λ below a cutoff wavelength λc over the unfilled 2D TaPhCs are demonstrated. The optimized designs possess high hemispherically average emittance/absorptance εH of 0.