Spiral scanning improves subject fixation in widefield retinal imaging.

Point scanning retinal imaging modalities, including confocal scanning light ophthalmoscopy (cSLO) and optical coherence tomography, suffer from fixational motion artifacts. Fixation targets, though effective at reducing eye motion, are infeasible in some applications (e.g., handheld devices) due to their bulk and complexity. Here, we report on a cSLO device that scans the retina in a spiral pattern under pseudo-visible illumination, thus collecting image data while simultaneously projecting, into the subject's vision, the image of a bullseye, which acts as a virtual fixation target. An imaging study of 14 young adult volunteers was conducted to compare the fixational performance of this technique to that of raster scanning, with and without a discrete inline fixation target. Image registration was used to quantify subject eye motion; a strip-wise registration method was used for raster scans, and a novel, to the best of our knowledge, ring-based method was used for spiral scans. Results indicate a statistically significant reduction in eye motion by the use of spiral scanning as compared to raster scanning without a fixation target.

Lymphatics in Tumor Progression and Immunomodulation.

The lymphatic system consists of a unidirectional hierarchy of vessels responsible for fluid homeostasis, lipid absorption, and the transport of immune cells and antigens to secondary lymphoid organs. In cancer, lymphatics play complex and heterogenous roles that can promote or inhibit tumor growth. While lymphatic proliferation and remodeling promote tumor dissemination, functional lymphatics are necessary for generating an effective immune response. Recent reports have noted lymphatic-dependent effects on the efficacy of immunotherapy. These findings suggest that the impact of lymphatic vessels on tumor progression is organ- and context-specific and that a greater understanding of the interaction of tumor cells, lymphatics, and the tumor microenvironment can unveil novel therapies.

Tumor-Associated Lymphatics Upregulate MHC-II to Suppress Tumor-Infiltrating Lymphocytes.

Steady-state lymphatic endothelial cells (LECs) can induce peripheral tolerance by presenting endogenous antigens on MHC class I (MHC-I) molecules. Recent evidence suggests that lymph node LECs can cross-present tumor antigens on MHC-I to suppress tumor-specific CD8+ T cells. Whether LECs can act as immunosuppressive cells in an MHC-II dependent manner in the local tumor microenvironment (TME) is not well characterized. Using murine heterotopic and spontaneous tumor models, we show that LECs in the TME increase MHC-II expression in the context of increased co-inhibitory signals. We provide evidence that tumor lymphatics in human melanoma and breast cancer also upregulate MHC-II compared to normal tissue lymphatics. In transgenic mice that lack LEC-specific MHC-II expression, heterotopic tumor growth is attenuated, which is associated with increased numbers of tumor-specific CD8+ and effector CD4+ T cells, as well as decreased numbers of T regulatory CD4+ cells in the TME. Mechanistically, we show that murine and human dermal LECs can take up tumor antigens in vitro. Antigen-loaded LECs in vitro can induce antigen-specific proliferation of CD8+ T cells but not CD4+ T cells; however, these proliferated CD8+ T cells have reduced effector function in the presence of antigen-loaded LECs. Taken together, our study suggests LECs can act as immunosuppressive cells in the TME in an MHC-II dependent manner. Whether this is a result of direct tumor antigen presentation on MHC-II requires additional investigation.

Strong, Hydrostable, and Degradable Straws Based on Cellulose-Lignin Reinforced Composites.

The huge consumption of single-use plastic straws has brought a long-lasting environmental problem. Paper straws, the current replacement for plastic straws, suffer from drawbacks, such as a high cost of the water-proof wax layer and poor water stability due to the easy delamination of the wax layer. It is therefore crucial to find a high-performing alternative to mitigate the environmental problems brought by plastic straws. In this paper, all natural, degradable, cellulose-lignin reinforced composite straws, inspired by the reinforcement principle of cellulose and lignin in natural wood are developed. The cellulose-lignin reinforced composite straw is fabricated by rolling up a wet film made of homogeneously mixed cellulose microfibers, cellulose nanofibers, and lignin powders, which is then baked in oven at 150 °C. When baked, lignin melts and infiltrates the micro-nanocellulose network, acting as a polyphenolic binder to improve the mechanical strength and hydrophobicity performance of the resulting straw. The obtained straws demonstrate several advantageous properties over paper straws, including 1) excellent mechanical performance, 2) high hydrostability, and 3) low cost. Moreover, the natural degradability of the cellulose-lignin reinforced composite straws makes them promising candidates to replace plastic straws and suggests possible substitutes for other petroleum-based plastics.

Hybrid modes in a single thermally excited asymmetric dimer antenna.

The study of hybrid modes in a single dimer of neighboring antennas is an essential step to optimize the far-field electromagnetic (EM) response of large-scale metasurfaces or any complex antenna structure made up of subwavelength building blocks. Here we present far-field infrared spatial modulation spectroscopy (IR-SMS) measurements of a single thermally excited asymmetric dimer of square metal-insulator-metal (MIM) antennas separated by a nanometric gap. Through thermal fluctuations, all the EM modes of the antennas are excited, and hybrid bonding and anti-bonding modes can be observed simultaneously. We study the latter within a plasmon hybridization model, and analyze their effect on the far-field response.

Histopathologic Features of Lymphedema: A Molecular Review.

An estimated 5 million people in the United States are affected by secondary lymphedema, with most cases attributed to malignancies or malignancy-related treatments. The pathogenesis of secondary lymphedema has historically been attributed to lymphatic injury or dysfunction; however, recent studies illustrate the complexity of lymphedema as a disease process in which many of its clinical features such as inflammation, fibrosis, adipogenesis, and recurrent infections contribute to on-going lymphatic dysfunction in a vicious cycle. Investigations into the molecular underpinning of these features further our understanding of the pathophysiology of this disease and suggests new therapeutics.

Decoupling Ionic and Electronic Pathways in Low-Dimensional Hybrid Conductors.

The construction of two-dimensional (2D) layered compounds for nanofluidic ion transport has recently attracted increasing interest due to the facile fabrication, tunable channel size, and high flux of these materials. Here we design a nacre-mimetic graphite-based nanofluidic structure in which the nanometer-thick graphite flakes are wrapped by negatively charged nanofibrillated cellulose (NFC) fibers to form multiple 2D confined spacings as nanochannels for rapid cation transport. At the same time, the graphite-NFC structure exhibits an ultralow electrical conductivity (σe ≤ 10-9 S/cm), even when the graphite concentration is up to 50 wt %, well above the percolation threshold (∼1 wt %). By tuning the hydration degree of graphite-NFC composites, the surface-charge-governed ion transport in the confined ∼1 nm spacings exhibits nearly 12 times higher ionic conductivity (1 × 10-3 S/cm) than that of a fully swollen structure (∼1.5 nm, 8.5 × 10-5 S/cm) at salt concentrations up to 0.1 M. The resulting charge selective conductor shows intriguing features of both high ionic conductivity and low electrical conductivity. Moreover, the inherent stability of the graphite and NFC components contributes to the strong functionality of the nanofluidic ion conductors in both acidic and basic environments. Our work demonstrates this 1D-2D material hybrid system as a suitable platform to study nanofluidic ion transport and provides a promising strategy to decouple ionic and electronic pathways, which is attractive for applications in new nanofluidic device designs.

Current treatment landscape for patients with locally recurrent inoperable or metastatic triple-negative breast cancer: a systematic literature review.

BACKGROUND: Metastatic triple-negative breast cancer (mTNBC), an aggressive histological subtype, has poor prognosis. Chemotherapy remains standard of care for mTNBC, although no agent has been specifically approved for this breast cancer subtype. Instead, chemotherapies approved for metastatic breast cancer (MBC) are used for mTNBC (National Comprehensive Cancer Network Guidelines [NCCN] v1.2019). Atezolizumab in combination with nab-paclitaxel was recently approved for programmed death-ligand 1 (PD-L1)-positive locally advanced or metastatic TNBC. Published historical data were reviewed to characterize the efficacy of NCCN-recommended (v1.2016) agents as first-line (1L) and second-line or later (2L+) treatment for patients with locally recurrent inoperable or metastatic TNBC (collectively termed mTNBC herein). METHODS: A systematic literature review was performed, examining clinical efficacy of therapies for mTNBC based on NCCN v1.2016 guideline recommendations. Data from 13 studies, either published retrospective mTNBC subgroup analyses based on phase III trials in MBC or phase II trials in mTNBC, were included. RESULTS: A meta-analysis of mTNBC subgroups from three phase III trials in 1L MBC reported pooled objective response rate (ORR) of 23%, median overall survival (OS) of 17.5 months, and median progression-free survival (PFS) of 5.4 months with single-agent chemotherapy. In two subgroup analyses from a phase III study and a phase II trial (n = 40 each), median duration of response (DOR) to 1L chemotherapy for mTNBC was 4.4-6.6 months; therefore, responses were not durable. A meta-analysis of seven cohorts showed the pooled ORR for 2L+ chemotherapy was 11% (95% CI, 9-14%). Median DOR to 2L+ chemotherapy in mTNBC was also limited (4.2-5.9 months) per two subgroup analyses from a phase III study. No combination chemotherapy regimens recommended by NCCN v1.2016 for treatment of MBC showed superior OS to single agents. CONCLUSIONS: Chemotherapies have limited effectiveness and are associated with unfavorable toxicity profiles, highlighting a considerable unmet medical need for improved therapeutic options in mTNBC. In addition to the recently approved combination of atezolizumab and nab-paclitaxel for PD-L1-positive mTNBC, new treatments resulting in durable clinical responses, prolonged survival, and manageable safety profile would greatly benefit patients with mTNBC.

Current Management and Future Opportunities for Peritoneal Metastases: Peritoneal Mesothelioma.

PURPOSE: Diffuse malignant peritoneal mesothelioma (MPM) is a rare and ultimately fatal cancer that was first described just over a century ago. It is a diffuse malignancy arising from the mesothelial lining of the peritoneum; morbidity and mortality from MPM is due to its propensity to progress locoregionally within the abdominal cavity. METHODS: The purpose of this article is to review the current state-of-the-science related to the diagnosis, staging, and treatment of MPM. RESULTS: The condition afflicts men and women equally and the peak incidence is between 55 and 60 years of age although it can arise in the young and elderly. Patients afflicted with MPM most commonly present with nonspecific abdominal symptoms that usually lead to diagnosis when the condition is relatively advanced. Historically, median overall survival for MPM patients without treatment is < 1 year. The couplet of systemic pemetrexed and cisplatin has an overall response rate of approximately 25% and a median overall survival of approximately 1 year. CONCLUSION: The available data, almost all retrospective in nature, have shown that in selected patients, operative cytoreduction (CRS) and regional chemotherapy administered as hyperthermic intraoperative peritoneal chemotherapy (HIPEC) or early postoperative intraperitoneal chemotherapy (EPIC) is associated with long-term survival. Studies on the molecular biology of MPM have yielded new insights relating to the potentially important role of the phosphoinsitide-3-kinase/mammalian target of rapamycin (PI3 K/mTOR) pathways and immune checkpoint inhibitors that may translate into new therapeutic options for patients with diffuse MPM.

Near-Field and Far-Field Thermal Emission of an Individual Patch Nanoantenna.

The far-field spectral and near-field spatial responses of an individual metal-insulator-metal nanoantenna are reported, using thermal fluctuations as an internal source of the electromagnetic field. The far-field spectra, obtained by combining Fourier transform infrared spectroscopy with spatial modulation based on a light falloff effect in a confocal geometry, have revealed two distinct emission peaks attributed to the excitation of the fundamental mode of the nanoantenna at two distinct wavelengths. Superresolved near-field images of the thermally excited mode have been obtained by thermal radiation scanning tunneling microscopy. Experimental results are supported by numerical simulations showing that it is possible to excite the same mode at different wavelengths near a resonance of the insulating dielectric material forming the antenna.

CYP3A5 genotype and its impact on vincristine pharmacokinetics and development of neuropathy in Kenyan children with cancer.

BACKGROUND: Vincristine (VCR) is a critical part of treatment in pediatric malignancies and is associated with dose-dependent peripheral neuropathy (vincristine-induced peripheral neuropathy [VIPN]). Our previous findings show VCR metabolism is regulated by the CYP3A5 gene. Individuals who are low CYP3A5 expressers metabolize VCR slower and experience more severe VIPN as compared to high expressers. Preliminary observations suggest that Caucasians experience more severe VIPN as compared to nonCaucasians. PROCEDURE: Kenyan children with cancer who were undergoing treatment including VCR were recruited for a prospective cohort study. Patients received IV VCR 2 mg/m2 /dose with a maximum dose of 2.5 mg as part of standard treatment protocols. VCR pharmacokinetics (PK) sampling was collected via dried blood spot cards and genotyping was conducted for common functional variants in CYP3A5, multi-drug resistance 1 (MDR1), and microtubule-associated protein tau (MAPT). VIPN was assessed using five neuropathy tools. RESULTS: The majority of subjects (91%) were CYP3A5 high-expresser genotype. CYP3A5 low-expresser genotype subjects had a significantly higher dose and body surface area normalized area under the curve than CYP3A5 high-expresser genotype subjects (0.28 ± 0.15 hr·m2 /l vs. 0.15 ± 0.011 hr·m2 /l, P = 0.027). Regardless of which assessment tool was utilized, minimal neuropathy was detected in this cohort. There was no difference in the presence or severity of neuropathy assessed between CYP3A5 high- and low-expresser genotype groups. CONCLUSION: Genetic factors are associated with VCR PK. Due to the minimal neuropathy observed in this cohort, there was no demonstrable association between genetic factors or VCR PK with development of VIPN. Further studies are needed to determine the role of genetic factors in optimizing dosing of VCR for maximal benefit.

Time dependent pharmacokinetics of pembrolizumab in patients with solid tumor and its correlation with best overall response.

Pembrolizumab is a monoclonal antibody that targets the programmed death-1 receptor to induce immune-mediated clearance (CL) of tumor cells. Originally approved by the US Food and Drug Administration in 2014 for treating patients with unresectable or metastatic melanoma, pembrolizumab is now also used to treat patients with non-small-cell lung cancer, classical Hodgkin lymphoma, head and neck cancer, and urothelial cancer. This paper describes the recently identified feature of pembrolizumab pharmacokinetics, the time-dependent or time-varying CL. Overall results indicate that CL decreases over the treatment period of a typical patient in a pattern well described by a sigmoidal function of time with three parameters: the maximum proportion change in CL from baseline (approximately Imax or exactly eImax - 1), the time to reach Imax/2 (TI50), and a Hill coefficient. Best overall response per response evaluation criteria in solid tumor category was found to be associated with the magnitude of Imax.

Prediction of brain clozapine and norclozapine concentrations in humans from a scaled pharmacokinetic model for rat brain and plasma pharmacokinetics.

BACKGROUND: Clozapine is highly effective in treatment-resistant schizophrenia, although, there remains significant variability in the response to this drug. To better understand this variability, the objective of this study was to predict brain extracellular fluid (ECF) concentrations and receptor occupancy of clozapine and norclozapine in human central nervous system by translating plasma and brain ECF pharmacokinetic (PK) relationships in the rat and coupling these with known human disposition of clozapine in the plasma. METHODS: Unbound concentrations of clozapine and norclozapine were measured in rat brain ECF using quantitative microdialysis after subcutaneous administration of a 10 mg/kg single dose of clozapine or norclozapine. These data were linked with plasma concentrations obtained in the same rats to develop a plasma-brain ECF compartmental model. Parameters describing brain ECF disposition were then allometrically scaled and linked with published human plasma PK to predict human ECF concentrations. Subsequently, prediction of human receptor occupancy at several CNS receptors was based on an effect model that related the predicted ECF concentrations to published concentration-driven receptor occupancy parameters. RESULTS: A one compartment model with first order absorption and elimination best described clozapine and norclozapine plasma concentrations in rats. A delay in the transfer of clozapine and norclozapine from plasma to the brain ECF compartment was captured using a transit compartment model approach. Human clozapine and norclozapine concentrations in brain ECF were simulated, and from these the median percentage of receptor occupancy of dopamine-2, serotonin-2A, muscarinic-1, alpha-1 adrenergic, alpha-2 adrenergic and histamine-1 for clozapine, and dopamine-2 for norclozapine were consistent with values reported in the literature. CONCLUSIONS: A PK model that relates clozapine and norclozapine disposition in rat plasma and brain, including blood-brain barrier transport, was developed. Using allometry and published human plasma PK, the model was successfully translated to predict clozapine and norclozapine concentrations and accordant receptor occupancy of both agents in human brain. These predicted exposure and occupancy measures at several receptors that bind clozapine may be employed to extend our understanding of clozapine's complex behavioral effects in humans.

Pharmacogenomics of gemcitabine metabolism: functional analysis of genetic variants in cytidine deaminase and deoxycytidine kinase.

Gemcitabine (dFdC, 2',2'-difluorodeoxycytidine) is metabolized by cytidine deaminase (CDA) and deoxycytidine kinase (DCK), but the contribution of genetic variation in these enzymes to the variability in systemic exposure and response observed in cancer patients is unclear. Wild-type enzymes and variants of CDA (Lys27Gln and Ala70Thr) and DCK (Ile24Val, Ala119Gly, and Pro122Ser) were expressed in and purified from Escherichia coli, and enzyme kinetic parameters were estimated for cytarabine (Ara-C), dFdC, and its metabolite 2',2'-difluorodeoxyuridine (dFdU) as substrates. All three CDA proteins showed similar K(m) and V(max) for Ara-C and dFdC deamination, except for CDA70Thr, which had a 2.5-fold lower K(m) and 6-fold lower V(max) for Ara-C deamination. All four DCK proteins yielded comparable metabolic activity for Ara-C and dFdC monophosphorylation, except for DCK24Val, which demonstrated an approximately 2-fold increase (P < 0.05) in the intrinsic clearance of dFdC monophosphorylation due to a 40% decrease in K(m) (P < 0.05). DCK did not significantly contribute to dFdU monophosphorylation. In conclusion, the Lys27Gln substitution does not significantly modulate CDA activity toward dFdC, and therefore would not contribute to interindividual variability in response to gemcitabine. The higher in vitro catalytic efficiency of DCK24Val toward dFdC monophosphorylation may be relevant to dFdC clinical response. The substrate-dependent alterations in activities of CDA70Thr and DCK24Val in vitro were observed for the first time, and demonstrate that the in vivo consequences of these genetic variations should not be extrapolated from one substrate of these enzymes to another.

Topical captopril: a promising treatment for secondary lymphedema.

Transforming growth factor-beta 1 (TGF-ß1)-mediated tissue fibrosis is an important regulator of lymphatic dysfunction in secondary lymphedema. However, TGF-ß1 targeting can cause toxicity and autoimmune complications, limiting clinical utility. Angiotensin II (Ang II) modulates intracellular TGF-ß1 signaling, and inhibition of Ang II production using angiotensin-converting enzyme (ACE) inhibitors, such as captopril, has antifibrotic efficacy in some pathological settings. Therefore, we analyzed the expression of ACE and Ang II in clinical lymphedema biopsy specimens from patients with unilateral breast cancer-related lymphedema (BCRL) and mouse models, and found that cutaneous ACE expression is increased in lymphedematous tissues. Furthermore, topical captopril decreases fibrosis, activation of intracellular TGF-ß1 signaling pathways, inflammation, and swelling in mouse models of lymphedema. Captopril treatment also improves lymphatic function and immune cell trafficking by increasing collecting lymphatic pumping. Our results show that the renin-angiotensin system in the skin plays an important role in the regulation of fibrosis in lymphedema, and inhibition of this signaling pathway may hold merit for treating lymphedema.

Treatment of Patients with Malignant Peritoneal Mesothelioma.

Malignant peritoneal mesothelioma is a rare malignancy arising from the serosa of the peritoneal cavity. It is diagnosed based on suspicious findings on cross sectional imaging and a tissue biopsy showing confirmatory histologic and immunohistochemical features. The disease is hallmarked by its propensity to progress mainly in the peritoneal cavity. In selected patients, surgical cytoreduction and hyperthermic intra-operative peritoneal chemotherapy has become the initial preferred treatment and is associated with provide prolonged in many patients. Systemic chemotherapy using a couplet of cisplatin or gemcitabine with pemetrexed has modest response rates and duration of response. Expression of PD-L1 has been demonstrated in peritoneal mesothelioma tumors and there has been significant interest in the use of check point blockade targeted against PD-L1 in this clinical setting. Future clinical research using a combination of check point blockade with surgical cytoreduction is a high clinical priority.

Population-based cellular kinetic characterization of ciltacabtagene autoleucel in subjects with relapsed or refractory multiple myeloma.

The aims of this work were to develop a population pharmacokinetic (PK) model for chimeric antigen receptor (CAR) transgene after single intravenous infusion administration of ciltacabtagene autoleucel in adult patients with relapsed or refractory multiple myeloma. CAR transgene level in blood were measured by quantitative polymerase chain reaction (qPCR) from 97 subjects in a phase Ib/II CARTITUDE-1 study (NCT03548207), with a targeted cilta-cel dose of 0.75 × 106 (range 0.5-1.0 × 106 ) CAR positive viable T-cells per kg body weight. The population PK model development was primarily guided by the current mechanistic understanding of CAR-T kinetics and the principles of building a parsimonious model. Cilta-cel PK was adequately described by a two-compartment model (with a fast and a slow apparent decline rate from each compartment, respectively) and a chain of four transit compartments with a lag time empirically representing the process from infused CAR-T cell to measurable CAR transgene. No apparent relationship was observed between cilta-cel dose (i.e., the actual number of CAR positive viable T-cells infused), given the narrow dose range, and the observed transgene level. Based on covariate search and subgroup analysis of maximum systemic CAR transgene level (Cmax ) and area under curve from the first dose to day 28 (AUC0-28d ), none of the investigated subjects' demographics, baseline characteristics, and manufactured product characteristics had significant effects on cilta-cel PK. The developed model is deemed robust and adequate for enabling subsequent exposure-safety and exposure-efficacy analyses.

Incidence and management of CAR-T neurotoxicity in patients with multiple myeloma treated with ciltacabtagene autoleucel in CARTITUDE studies.

Chimeric antigen receptor (CAR) T-cell therapies are highly effective for multiple myeloma (MM) but their impressive efficacy is associated with treatment-related neurotoxicities in some patients. In CARTITUDE-1, 5% of patients with MM reported movement and neurocognitive treatment-emergent adverse events (MNTs) with ciltacabtagene autoleucel (cilta-cel), a B-cell maturation antigen-targeted CAR T-cell therapy. We assessed the associated factors for MNTs in CARTITUDE-1. Based on common features, patients who experienced MNTs were characterized by the presence of a combination of at least two variables: high tumor burden, grade ≥2 cytokine release syndrome (CRS) or any grade immune effector cell-associated neurotoxicity syndrome (ICANS) after cilta-cel infusion, and high CAR T-cell expansion/persistence. Strategies were implemented across the cilta-cel development program to monitor and manage patients with MNTs, including enhanced bridging therapy to reduce baseline tumor burden, early aggressive treatment of CRS and ICANS, handwriting assessments for early symptom detection, and extended monitoring/reporting time for neurotoxicity beyond 100 days post-infusion. After successful implementation of these strategies, the incidence of MNTs was reduced from 5% to <1% across the cilta-cel program, supporting its favorable benefit-risk profile for treatment of MM.

Experimental Medicine Study to Measure Immune Checkpoint Receptors PD-1 and GITR Turnover Rates In Vivo in Humans.

Development of monoclonal antibodies (mAbs) targeting immune-checkpoint receptors (IMRs) for the treatment of cancer is one of the most active areas of investment in the biopharmaceutical industry. A key decision in the clinical development of anti-IMR mAbs is dose selection. Dose selection can be challenging because the traditional oncology paradigm of administering the maximum tolerated dose is not applicable to anti-IMR mAbs. Instead, dose selection should be informed by the pharmacology of immune signaling. Engaging an IMR is a key initial step to triggering pharmacologic effects, and turnover (i.e., the rate of protein synthesis) of the IMR is a key property to determining the dose level needed to engage the IMR. Here, we applied the stable isotope labeling mass spectrometry technique using 13 C6 -leucine to measure the in vivo turnover rates of IMRs in humans. The 13 C6 -leucine was administered to 10 study participants over 15 hours to measure 13 C6 -leucine enrichment kinetics in 2 IMR targets that have been clinically pursued in oncology: GITR and PD-1. We report the first measurements of GITR and PD-1 median half-lives associated with turnover to be 55.6 and ≥ 49.5 hours, respectively. The approach outlined here can be applied to other IMRs and, more generally, to protein targets.

Pilot Study of Anti-Th2 Immunotherapy for the Treatment of Breast Cancer-Related Upper Extremity Lymphedema.

Recent studies suggest that Th2 cells play a key role in the pathology of secondary lymphedema by elaborating cytokines such as IL4 and IL13. The aim of this study was to test the efficacy of QBX258, a monoclonal IL4/IL13 neutralizing antibody, in women with breast cancer-related lymphedema (BCRL). We enrolled nine women with unilateral stage I/II BCRL and treated them once monthly with intravenous infusions of QBX258 for 4 months. We measured limb volumes, bioimpedance, and skin tonometry, and analyzed the quality of life (QOL) using a validated lymphedema questionnaire (Upper Limb Lymphedema 27, ULL-27) before treatment, immediately after treatment, and 4 months following treatment withdrawal. We also obtained 5 mm skin biopsies from the normal and lymphedematous limbs before and after treatment. Treatment was well-tolerated; however, one patient with a history of cellulitis developed cellulitis during the trial and was excluded from further analysis. We found no differences in limb volumes or bioimpedance measurements after drug treatment. However, QBX258 treatment improved skin stiffness (p < 0.001) and improved QOL measurements (Physical p < 0.05, Social p = 0.01). These improvements returned to baseline after treatment withdrawal. Histologically, treatment decreased epidermal thickness, the number of proliferating keratinocytes, type III collagen deposition, infiltration of mast cells, and the expression of Th2-inducing cytokines in the lymphedematous skin. Our limited study suggests that immunotherapy against Th2 cytokines may improve skin changes and QOL of women with BCRL. This treatment appears to be less effective for decreasing limb volumes; however, additional studies are needed.