Comprehensive single institute experience with melanoma TIL: Long term clinical results, toxicity profile, and prognostic factors of response.

Adoptive cell transfer (ACT) of tumor-infiltrating lymphocytes (TIL) mediates objective responses in 30% to 50% of patients with metastatic melanoma according to multiple, small phase 2 trials. Here we report the long-term clinical results, intent-to-treat analysis, predictors of response and toxicity profile in a large patient cohort. A total of 179 refractory melanoma patients were enrolled in the ACT trial.

Locally produced CD19 CAR T cells leading to clinical remissions in medullary and extramedullary relapsed acute lymphoblastic leukemia.

Autologous CD19 chimeric-antigen receptor (CAR) T cells demonstrated remarkable remission rates in relapsed and refractory acute lymphoblastic leukemia (R/R ALL). Here, we report results from a phase 1b/2 study of in-house produced CD19 CAR with a CD28 costimulatory domain. Twenty-one patients with R/R ALL were enrolled, and 20 infused.

An improved design of optical sensor for long-term measurement of arterial blood flow waveform.

We present here the improved design and development of optical sensor for non-invasive measurements of arterial blood flow waveform. The sensor is based on a physical principle of reflective photoplethysmography (PPG). As the light source we used serially connected infrared diodes whereas NPN silicon phototransistors were used as light detectors.

Predictors of tumor-infiltrating lymphocyte efficacy in melanoma.

In the past decades, the increasing knowledge in cellular immunology and tumor-host immune interactions, led to the development of immunotherapy approaches. Immunotherapy, based on adoptive cell transfer of ex vivo activated and expanded tumor-infiltrating T lymphocytes (TILs), has shown promising clinical results in patients with metastatic melanoma. TIL therapy yields response rates of around 50% and significant survival benefit in refractory melanoma patients, even after failing other immunotherapies, such as checkpoint inhibitors or cytokine-based therapy.

Effect of viscosity on the wave propagation: Experimental determination of compression and expansion pulse wave velocity in fluid-fill elastic tube.

The velocity by which the disturbance travels through the medium is the wave velocity. Pulse wave velocity is one of the main parameters in hemodynamics. The study of wave propagation through the fluid-fill elastic tube is of great importance for the proper biophysical understanding of the nature of blood flow through of cardiovascular system.

A comparative analysis of total serum miRNA profiles identifies novel signature that is highly indicative of metastatic melanoma: a pilot study.

Context: Quantification of circulating microRNAs (miRNAs) has recently become feasible and reliable, with most efforts focusing on miRNAs overexpressed by cancer cells.

Objective: Identification of a characteristic circulating miRNAs profile in melanoma patients.

Methods: We conducted a pilot study comprised of unbiased qPCR comparison of serum miRNA profiles between metastatic melanoma patients and healthy donors.

Adoptive transfer of tumor-infiltrating lymphocytes in patients with metastatic melanoma: intent-to-treat analysis and efficacy after failure to prior immunotherapies.

Purpose: Adoptive cell transfer (ACT) using autologous tumor-infiltrating lymphocytes (TIL) was reported to yield objective responses in about 50% of metastatic patients with melanoma. Here, we present the intent-to-treat analysis of TIL ACT and analyze parameters predictive to response as well as the impact of other immunotherapies.

Experimental Design: Eighty patients with stage IV melanoma were enrolled, of which 57 were treated with unselected/young TIL and high-dose interleukin-2 (IL-2) following nonmyeloablative lymphodepleting conditioning.

Immunotherapy for the management of advanced melanoma: the next steps.

Melanoma is an immunogenic tumor that can induce a natural immune response. A number of immunotherapy-based approaches have been developed over the past decades, and certain degrees of effectiveness were achieved by the use of cytokines, adoptive cell transfer and T-cell immune modulators. Currently, interleukin-2 and the immune stimulatory antibody, ipilimumab, are the only two approved immunotherapies for metastatic melanoma, but various new therapies are in promising developmental stages.

Adoptive T-cell transfer in melanoma.

Immunotherapy holds a highly promising treatment approach for metastatic melanoma patients. Adoptive cell transfer (ACT) involves the ex vivo expansion of autologous antitumor reactive lymphocytes and their reinfusion into lymphodepleted patients, accompanied by IL-2 administration. ACT with tumor-infiltrating T lymphocytes demonstrates objective clinical responses in 50-72% of the patients, including 10-40% complete responses and was shown to produce durable disease control with long progression-free survival.

I-motif nanospheres: unusual self-assembly of long cytosine strands.

The synthesis and characterization of novel DNA structures based on tetraplex cytosine (C) arrangements, known as i-motifs or i-tetraplexes, is reported. Atomic force microscopy (AFM) investigation shows that long C-strands in mild acidic conditions form compact spherically shaped nanostructures. The DNA nanospheres are characterized by a typical uniform shape and narrow height distribution.

Establishment and large-scale expansion of minimally cultured "young" tumor infiltrating lymphocytes for adoptive transfer therapy.

Treatment of metastatic melanoma patients with adoptively transferred tumor infiltrating lymphocytes (TIL) has developed into an effective therapy. Various studies reported objective responses of 50% and more. The use of unselected, minimally cultured, bulk TIL (Young-TIL) has simplified the TIL production process and may therefore, allow the accessibility of this approach to cancer centers worldwide.

Long-lived fluorescence of homopolymeric guanine-cytosine DNA duplexes.

The fluorescence spectrum of the homopolymeric double helix poly(dG) x poly(dC) is dominated by emission decaying on the nanosecond time-scale, as previously reported for the alternating homologue poly(dGdC) x poly(dGdC). Thus, energy trapping over long periods of time is a common feature of GC duplexes which contrast with AT duplexes. The impact of such behaviour on DNA photodamage needs to be evaluated.

Specific high-affinity binding of thiazole orange to triplex and G-quadruplex DNA.

Interaction of Thiazole Orange (TO) with double-, triple-, and quadruple-stranded forms of DNA was studied. We have demonstrated by UV-vis absorption, circular dichroism (CD), and fluorescence spectroscopy that TO binds with much higher affinity to triplex and G-quadruplex DNA structures compared to double-stranded (ds) DNA. Complexes of the dye with DNA triplexes and G-quadruplexes are very stable and do not dissociate during chromatography and gel electrophoresis.

Synthesis and AFM characterization of poly(dG)-poly(dC)-gold nanoparticle conjugates.

In the present work, we have synthesized conjugates between the 5 nm gold nanoparticles (Au-NP) and 5' thiol-functionalized, 700 bp poly(dG)-poly(dC). We have completely separated and purified to homogeneity conjugates bearing different number of poly(dG)-poly(dC) molecules per Au-NP by electrophoresis and HPLC. The conjugates were directly visualized by atomic force microscopy.

Assembling of G-strands into novel tetra-molecular parallel G4-DNA nanostructures using avidin-biotin recognition.

We describe a method for the preparation of novel long (hundreds of nanometers), uniform, inter-molecular G4-DNA molecules composed of four parallel G-strands. The only long continuous G4-DNA reported so far are intra-molecular structures made of a single G-strand. To enable a tetra-molecular assembly of the G-strands we developed a novel approach based on avidin-biotin biological recognition.

Vesicle priming and recruitment by ubMunc13-2 are differentially regulated by calcium and calmodulin.

Ca2+ regulates multiple processes in nerve terminals, including synaptic vesicle recruitment, priming, and fusion. Munc13s, the mammalian homologs of Caenorhabditis elegans Unc13, are essential vesicle-priming proteins and contain multiple regulatory domains that bind second messengers such as diacylglycerol and Ca2+/calmodulin (Ca2+/CaM). Binding of Ca2+/CaM is necessary for the regulatory effect that allows Munc13-1 and ubMunc13-2 to promote short-term synaptic plasticity.