Long-term prevention of hereditary angioedema attacks with lanadelumab in adolescents.

BACKGROUND: Lanadelumab was well-tolerated and effective in preventing hereditary angioedema (HAE) attacks in the phase 3, double-blind, placebo-controlled HELP Study and subsequent open-label extension study, HELP OLE (NCT02741596). OBJECTIVE: To evaluate outcomes from HELP OLE for adolescent patients aged 12 to 17 years. METHODS: HELP OLE comprised patients who completed the HELP Study (rollovers) and new eligible (lanadelumab-naive) patients. Rollovers received a single dose of lanadelumab 300 mg at the last HELP Study visit (day 0). Treatment was then paused until patients experienced their first investigator-confirmed HAE attack, following which lanadelumab 300 mg was administered every 2 weeks (Q2W) for up to 33 months (4 weeks/month). Lanadelumab-naive patients received lanadelumab 300 mg Q2W from day 0. Patient-reported outcomes included Angioedema Quality of Life Questionnaire (AE-QoL). Safety was monitored throughout the study. RESULTS: The subgroup analysis included 21 patients (8 rollovers, 13 lanadelumab-naive patients); 95.2% completed ≥ 30 months on study. Mean (SD) monthly attack rates decreased from 1.58 (1.0) at baseline to 0.11 (0.2) during treatment (mean 94.7% reduction). Eight (38.1%) patients were attack-free during treatment and, on average, 99.1% of days were attack-free (mean 27.7 days/month). Patients reported a mean (SD) AE-QoL total score of 27.5 (17.5) at baseline vs 7.5 (13.2) at end of study. Twelve (57.1%) patients reported treatment-related treatment-emergent adverse events; however, there were no treatment-related serious adverse events. CONCLUSION: Lanadelumab provided long-term efficacy in preventing HAE attacks, was associated with clinically meaningful improvements in health-related quality of life and high levels of treatment satisfaction, and was well-tolerated in adolescent patients.

Dynamic mechanisms that couple the brain and breathing to the external environment.

Brain and breathing activities are closely related. However, the exact neurophysiological mechanisms that couple the brain and breathing to stimuli in the external environment are not yet agreed upon. Our data support that synchronization and dynamic attunement are two key mechanisms that couple local brain activity and breathing to external periodic stimuli. First, we review the existing literature, which provides strong evidence for the synchronization of brain and breathing in terms of coherence, cross-frequency coupling and phase-based entrainment. Second, using EEG and breathing data, we show that both the lungs and localized brain activity at the Cz channel attune the temporal structure of their power spectra to the periodic structure of external auditory inputs. We highlight the role of dynamic attunement in playing a key role in coordinating the tripartite temporal alignment of localized brain activity, breathing and input dynamics across longer timescales like minutes. Overall, this perspective sheds light on potential mechanisms of brain-breathing coupling and its alignment to stimuli in the external environment.

Hemospray® (hemostatic powder TC-325) as monotherapy for acute gastrointestinal bleeding: a multicenter prospective study.

Background: Hemostatic powders are used as second-line treatment in acute gastrointestinal (GI) bleeding (AGIB). Increasing evidence supports the use of TC-325 as monotherapy in specific scenarios. This prospective, multicenter study evaluated the performance of TC-325 as monotherapy for AGIB. Methods: Eighteen centers across Europe and USA contributed to a registry between 2016 and 2022. Adults with AGIB were eligible, unless TC-325 was part of combined hemostasis. The primary endpoint was immediate hemostasis. Secondary outcomes were rebleeding and mortality. Associations with risk factors were investigated (statistical significance at P≤0.05). Results: One hundred ninety patients were included (age 51-81 years, male: female 2:1), with peptic ulcer (n=48), upper GI malignancy (n=79), post-endoscopic treatment hemorrhage (n=37), and lower GI lesions (n=26). The primary outcome was recorded in 96.3% (95% confidence interval [CI]: 92.6-98.5) with rebleeding in 17.4% (95%CI 11.9-24.1); 9.9% (95%CI 5.8-15.6) died within 7 days, and 21.7% (95%CI 15.6-28.9) within 30 days. Regarding peptic ulcer, immediate hemostasis was achieved in 88% (95%CI 75-95), while 26% (95%CI 13-43) rebled. Higher ASA score was associated with mortality (OR 23.5, 95%CI 1.60-345; P=0.02). Immediate hemostasis was achieved in 100% of cases with malignancy and post-intervention bleeding, with rebleeding in 17% and 3.1%, respectively. Twenty-six patients received TC-325 for lower GI bleeding, and in all but one the primary outcome was achieved. Conclusions: TC-325 monotherapy is safe and effective, especially in malignancy or post-endoscopic intervention bleeding. In patients with peptic ulcer, it could be helpful when the primary treatment is unfeasible, as bridge to definite therapy.

Physician- and patient-reported outcomes by hereditary angioedema type: Data from a real-world study.

Background: Hereditary angioedema (HAE) is a rare genetic condition characterized by painful and often debilitating swelling attacks. Little is known about the differences in outcomes between patients with HAE types I or II (type I: HAE caused by C1 esterase inhibitor deficiency; type II: HAE caused by C1 esterase inhibitor dysfunction), with decreased or dysfunctional C1 esterase inhibitor (C1-INH), and those with normal C1-INH (nC1-INH-HAE). Objective: To compare physician- and patient-reported real-world outcomes in patients with HAE types I/II versus patients with nC1-INH-HAE. Methods: Data were drawn from the Adelphi HAE Disease Specific ProgrammeTM a real-world, cross-sectional survey of HAE-treating physicians and their patients in the United States conducted between July and November 2021. Physicians reported patient disease activity and severity, and recent attack history. Patient-reported outcomes were collected. Bivariate tests used were either the Student's t-test, the Fisher exact test, or Mann-Whitney U test. Results: Physicians (N = 67) provided data on 368 patients (92.4% HAE types I/II and 7.6% nC1-INH-HAE). Physicians reported that a higher proportion of patients with nC1-INH-HAE had moderate or high disease activity and moderate or severe disease severity both at diagnosis and at data collection versus those with HAE types I/II. Patients with nC1-INH-HAE versus patients with HAE types I/II experienced increased attack severity (34.6% versus 4.4%) and hospitalization rate during the most recent attack (39.3% versus 6.6%), and reported lower health status and quality of life, via the European Quality of Life 5 Dimension 5 Level (US tariff) and Angioedema Quality of Life, respectively. On average, 25% of the patients with nC1-INH-HAE reported absenteeism and work or activity impairment due to HAE compared with 2.7% of patients with HAE types I/II. Both patient groups reported improvements in disease activity and severity from diagnosis to the time of data collection. Conclusion: These real-world findings suggest that patients with nC1-INH-HAE have increased disease activity and severity, and experience greater impairment to their quality of life, work, and daily functioning than patients with HAE types I/II. Powered statistical analyses are required to confirm these findings.

Implementing a Halo Gravity Traction Program: A Multidisciplinary Endeavor.

Halo gravity traction (HGT) is a preoperative modality for children with severe spinal deformity used to optimize spine flexibility and balance while decreasing the likelihood of neurologic injury. HGT is a dependable solution for these challenging spinal deformities. Aligning treatment guidelines and providing resources, education, and training for staff are key components for a successful HGT program. The HGT program at Children's Mercy Hospital was then developed with a systems approach with the holistic goal of multidisciplinary collaboration with physical/occupational therapy, hospital medicine, pulmonology, psychology, nutrition, child life, and complex care management. Education, research, and national collaboration to standardize this therapy should improve patient safety and support quality improvement.

Summary and Panel Discussion.

In this video, Javed Butler, MD, Jonathan Rich, MD, Rachel Pessah-Pollack, MD, and John E. Anderson, MD, summarize the key points of the enhanced publication "Role of SGLT2 Inhibitors in the Management of Heart Failure With and Without Type 2 Diabetes." The panel then delves deeper into some of the topics raised.

Variable Peripheral Ligand Donation Tunes Electronic Structure and NIR II Emission in Tetrathiafulvalene Tetrathiolate Diradicaloids.

Near-infrared (NIR) lumiphores are promising candidates for numerous imaging, communication, and sensing applications, but they typically require large, conjugated scaffolds to achieve emission in this low-energy region. Due to the extended conjugation and synthetic complexity required, it is extremely difficult to tune the photophysical properties of these systems for desired applications. Here, we report facile tuning of deep NIR-emitting diradicaloid complexes through simple modification of peripheral ligands. These new lumiphores are rare examples of air-, acid-, and water-stable emissive diradicaloids. We apply a simple Hammett parameter-based strategy to tune the electron donation of the capping ligand across a series of commercially available triarylphosphines. This minor peripheral modification significantly alters the electronic structure, and consequently, the electrochemical, photophysical, and magnetic properties of the tetrathiafulvalene tetrathiolate (TTFtt)-based lumiphores. The resultant ∼100 nm absorption and emission range spans common laser lines and the desirable telecom region (ca. 1260-1550 nm). Furthermore, these lumiphores are sensitive to local dielectrics, distinguishing them as promising candidates for ratiometric imaging and/or barcoding in the deep NIR region.

Predictors of Concussion Symptom Reporting Intention among Collegiate Athletes.

CONTEXT: Underreporting of concussion symptoms in college athletics presents a challenge for sports medicine clinicians in evaluating and diagnosing such injuries. Some athletes do not report concussion symptoms because they do not recognize that they have a brain injury, however many athletes intentionally withhold symptoms to avoid removal from sport participation. OBJECTIVE: To examine individual factors that influence college athletes' intentions to report concussion symptoms. DESIGN: Cross-sectional study. SETTING: Collegiate athletics. PARTICIPANTS: 2,649 student-athletes from 23 sports, across 22 colleges/universities. MAIN OUTCOME MEASURES: The primary outcome was intention to report concussion symptoms. Predictor variables included demographics (age, race/ethnicity, sex, sport type, number of years in sport, number of previous concussions, and perceived concussion symptom knowledge), athletic identity, attitudes toward symptom reporting, perceived social pressure (injunctive and descriptive norms), and perceived behavioral control (capacity and autonomy). RESULTS: Hierarchical ordinary least squares regression revealed positive effects of attitude (b = .063; P = .005), descriptive norms (b = .131; P < .001), injunctive norms (b = .107; P < .001), and capacity (b = .196; P < .001) on intention to report symptoms. Athletic identity and participation in collision sports had small negative indirect effects on intention, while perceived concussion knowledge had a small positive indirect effect. The full regression model explained 14.24% of the variance in concussion reporting intention. CONCLUSIONS: These findings may help clinicians develop more focused interventions that address key social and individual determinants of underreporting, including attitude, injunctive and descriptive norms, and capacity to report. Athletic identity, sport type, and perceived understanding of concussion symptoms also influence reporting intention to a lesser extent. Previous research in this area has often failed to address a diverse population of college-age athletes from different sports and NCAA divisions.

Microbial reduction of prebagged human plasma using 405 nm light and its effects on coagulation factors.

Bacterial contamination is the most prevalent infectious complication of blood transfusion in the developed world. To mitigate this, several ultraviolet light-based pathogen reduction technologies (PRTs), some of which require photo-chemicals, have been developed to minimize infection transmission. Relative to UV light, visible 405-nm light is safer and has shown potential to be developed as a PRT for the in situ treatment of ex vivo human plasma and platelet concentrates, without the need for photo-chemicals. This study investigates the effect of 405-nm light on human plasma, with focus on the compatibility of antimicrobial light doses with essential plasma clotting factors. To determine an effective antimicrobial dose that is compatible with plasma, prebagged human plasma (up to 300 mL) was seeded with common microbial contaminants and treated with increasing doses of 405-nm light (16 mW cm-2; ≤ 403 J cm-2). Post-exposure plasma protein integrity was investigated using an AOPP assay, in vitro coagulation tests, and ELISA-based measurement of fibrinogen and Protein S. Microbial contamination in 300 mL prebagged human plasma was significantly reduced (P ≤ 0.05) after exposure to ≤ 288 J cm-2, with microbial loads reduced by > 96.2%. This dose did not significantly affect the plasma protein quality parameters tested (P > 0.05). Increased doses (≥ 345 J cm-2) resulted in a 4.3% increase in clot times with no statistically significant change in protein activity or levels. Overall, this study has demonstrated that the effective microbicidal 405 light dose shows little to no negative effect on plasma quality.

DCRM 2.0: Multispecialty practice recommendations for the management of diabetes, cardiorenal, and metabolic diseases.

The spectrum of cardiorenal and metabolic diseases comprises many disorders, including obesity, type 2 diabetes (T2D), chronic kidney disease (CKD), atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), dyslipidemias, hypertension, and associated comorbidities such as pulmonary diseases and metabolism dysfunction-associated steatotic liver disease and metabolism dysfunction-associated steatohepatitis (MASLD and MASH, respectively, formerly known as nonalcoholic fatty liver disease and nonalcoholic steatohepatitis [NAFLD and NASH]). Because cardiorenal and metabolic diseases share pathophysiologic pathways, two or more are often present in the same individual. Findings from recent outcome trials have demonstrated benefits of various treatments across a range of conditions, suggesting a need for practice recommendations that will guide clinicians to better manage complex conditions involving diabetes, cardiorenal, and/or metabolic (DCRM) diseases. To meet this need, we formed an international volunteer task force comprising leading cardiologists, nephrologists, endocrinologists, and primary care physicians to develop the DCRM 2.0 Practice Recommendations, an updated and expanded revision of a previously published multispecialty consensus on the comprehensive management of persons living with DCRM. The recommendations are presented as 22 separate graphics covering the essentials of management to improve general health, control cardiorenal risk factors, and manage cardiorenal and metabolic comorbidities, leading to improved patient outcomes.

Managing Patients on SGLT2 Inhibitors in Primary Care.

In this video, Javed Butler, MD, and John E. Anderson, MD, discuss the management of patients on SGLT2 inhibitors in the primary care setting.

Two AIS Cases, 2 Surgeons, 1 Operating Room, 1 Day: Faster and Safer Than 1 Case in a Day.

BACKGROUND: To lessen surgical times for patients with adolescent idiopathic scoliosis (AIS) undergoing posterior spinal instrumentation and fusion (PSIF), our department developed a quality improvement initiative where 2 AIS cases were completed in 1 day by the same 2 surgeons operating together in 1 operating room (OR). We describe the results of this initiative, comparing operative times and outcomes to cases of these surgeons operating individually. METHODS: From 2017 to 2023, patients aged 10 to 18 years with AIS undergoing PSIF were prospectively enrolled for "Two Spine Tuesday." Patients were matched by age, sex, curve severity, and number of levels fused to historical AIS controls. Outcomes included surgery time, total OR time, estimated blood loss (EBL), volume of cell saver transfused, allogenic blood transfusion, length of stay, 90-day readmissions, Clavien-Dindo-Sink Complication Classification System complication rates, and percentage who achieved the minimal clinically important difference (MCID) for SRS-22. RESULTS: Fifty-five patients composing the 2-spine group (group 2) were compared with 55 historical sex-matched and age-matched controls (group 1). Major coronal curve and average number of levels fused were similar between groups. Overall surgery time (203 vs. 296 min, P <0.001), total OR time ( P <0.001), and EBL (400 vs. 550 mL, P <0.001) were lower for group 2. Group 2 had fewer complications [n=17 (31%) vs. n=28 (51%), P =0.03]. CONCLUSIONS: Performing 2 AIS cases in 1 OR by 2 surgeons the same day resulted in shorter surgery times, less total time in the operating room, lower complication rates, and less blood loss compared with single-surgeon matched controls. LEVEL OF EVIDENCE: Level III-retrospective comparative study.

Metal-ligand cooperativity in chemical electrosynthesis.

Electrochemistry has been an increasingly useful tool for organic synthesis, as it can selectively generate reactive intermediates under mild conditions using an applied potential. Concurrently, synergistic activity of a metal and a ligand has been used in thermal catalysis and electrocatalytic renewable fuel generation for substrate selectivity and improved catalyst activity. Combining these synthetic strategies is an attractive approach for mild, selective, and sustainable electrosynthesis. This perspective discusses examples of metal-ligand synergistic catalysis in electrochemical applications in organic and organometallic synthesis. The range of reactions and ligand design principles illustrates many opportunities for further discovery in this area and the potential for far-reaching synthetic benefits.

Interspecies conflict, precarious reasoning, and the gull problem in the Gulf of Maine.

Contemporary conservation science requires mediating conflicts among nonhuman species, but the grounds for favoring one species over another can be unclear. We examined the premises through which wildlife managers picked sides in an interspecies conflict: seabird conservation in the Gulf of Maine (GOM). Managers in the GOM follow a simple narrative dubbed the gull problem. This narrative assumes Larus gulls are overpopulated and unnatural in the region. In turn, these assumptions make gulls an easy target for culling and lethal control when the birds come into conflict with other seabirds, particularly Sterna terns. Surveying historical, natural historical, and ecological evidence, we found no scientific support for the claim that Larus gulls are overpopulated in the GOM. Claims of overpopulation originated from a historical context in which rising gull populations became a nuisance to humans. Further, we found only limited evidence that anthropogenic subsidies make gulls unnatural in the region, especially when compared with anthropogenic subsidies provided for other seabirds. The risks and consequences of leveraging precarious assumptions include cascading plans to cull additional gull populations, obfuscation of more fundamental environmental threats to seabirds, and the looming paradox of gull conservation-even if one is still inclined to protect terns in the GOM. Our close look at the regional history of a conservation practice thus revealed the importance of not only conservation decisions, but also conservation decision-making.

Conflicto interespecífico, razonamiento precario y el problema de las gaviotas en el Golfo de Maine Resumen La ciencia de la conservación actual requiere mediar conflictos entre las especies no humanas, pero los fundamentos para favorecer a una especie por encima de otra pueden ser poco claros. Analizamos las premisas mediante las cuales los gestores de fauna eligen bandos en un conflicto interespecífico: la conservación de aves marinas en el Golfo de Maine (GDM). Los gestores en el GDM siguen una narrativa simple llamada el problema de las gaviotas. Esta narrativa asume que las gaviotas del género Larus no son nativas y tienen una sobrepoblación en la región. En cambio, estas suposiciones hacen que las gaviotas sean un objetivo fácil para el sacrificio y el control letal cuando las aves entran en conflicto con otras aves marinas, en particular con los charranes del género Sterna. Censamos la evidencia histórica, ecológica y de historia natural y no encontramos respaldo científico alguno para la afirmación de que hay una sobrepoblación de gaviotas Larus en el GDM. Esta afirmación se originó a partir de un contexto histórico en el que el incremento poblacional de las gaviotas se volvió una molestia para los humanos. Además, encontramos evidencia limitada de que los subsidios antropogénicos hacen que las gaviotas no sean nativas en la región, en especial cuando los comparamos con los subsidios antropogénicos proporcionados a otras aves marinas. Los riesgos y consecuencias de impulsar suposiciones precarias incluyen los planes en cascada para sacrificar poblaciones adicionales de gaviotas, la ofuscación de amenazas ambientales más fundamentales para las aves marinas y la paradoja inminente de la conservación de las gaviotas­incluso si todavía se inclinan por proteger a los charranes en el GDM. Esta mirada detallada de la historia regional de una práctica de conservación nos reveló la importancia no sólo de las decisiones de conservación, sino también de la toma de decisiones de conservación.

Tracking the Cognitive Band in an Open-Ended Task.

Open-ended tasks can be decomposed into the three levels of Newell's Cognitive Band: the Unit-Task level, the Operation level, and the Deliberate-Act level. We analyzed the video game Co-op Space Fortress at these levels, reporting both the match of a cognitive model to subject behavior and the use of electroencephalogram (EEG) to track subject cognition. The Unit Task level in this game involves coordinating with a partner to kill a fortress. At this highest level of the Cognitive Band, there is a good match between subject behavior and the model. The EEG signals were also strong enough to track when Unit Tasks succeeded or failed. The intermediate Operation level in this task involves legs of flight to achieve a kill. The EEG signals associated with these operations are much weaker than the signals associated with the Unit Tasks. Still, it was possible to reconstruct subject play with much better than chance success. There were significant differences in the leg behavior of subjects and models. Model behavior did not provide a good basis for interpreting a subject's behavior at this level. At the lowest Deliberate-Act level, we observed overlapping key actions, which the model did not display. Such overlapping key actions also frustrated efforts to identify EEG signals of motor actions. We conclude that the Unit-task level is the appropriate level both for understanding open-ended tasks and for using EEG to track the performance of open-ended tasks.

UV damage induces production of mitochondrial DNA fragments with specific length profiles.

UV light is a potent mutagen that induces bulky DNA damage in the form of cyclobutane pyrimidine dimers (CPDs). Photodamage and other bulky lesions occurring in nuclear genomes can be repaired through nucleotide excision repair (NER), where incisions on both sides of a damaged site precede the removal of a single-stranded oligonucleotide containing the damage. Mitochondrial genomes (mtDNAs) are also susceptible to damage from UV light, but current evidence suggests that the only way to eliminate bulky mtDNA damage is through mtDNA degradation. Damage-containing oligonucleotides excised during NER can be captured with antidamage antibodies and sequenced (XR-seq) to produce high-resolution maps of active repair locations following UV exposure. We analyzed previously published datasets from Arabidopsis thaliana, Saccharomyces cerevisiae, and Drosophila melanogaster to identify reads originating from the mtDNA (and plastid genome in A. thaliana). In A. thaliana and S. cerevisiae, the mtDNA-mapping reads have unique length distributions compared to the nuclear-mapping reads. The dominant fragment size was 26 nt in S. cerevisiae and 28 nt in A. thaliana with distinct secondary peaks occurring in regular intervals. These reads also show a nonrandom distribution of di-pyrimidines (the substrate for CPD formation) with TT enrichment at positions 7-8 of the reads. Therefore, UV damage to mtDNA appears to result in production of DNA fragments of characteristic lengths and positions relative to the damaged location. The mechanisms producing these fragments are unclear, but we hypothesize that they result from a previously uncharacterized DNA degradation pathway or repair mechanism in mitochondria.

Transiliac-Shortening Osteotomy to Treat Ischial Pressure Injury due to Fixed Pelvic Obliquity: A Case Report.

CASE: A 17-year-old adolescent boy with Gross Motor Function Classification System 5 cerebral palsy and neuromuscular scoliosis underwent posterior spinal fusion and segmental spinal instrumentation from T3 to the pelvis. He developed a right ischial pressure injury a few months postoperatively, which persisted despite nonoperative measures. He subsequently underwent an ipsilateral transiliac-shortening osteotomy 16 months after spinal surgery to treat his residual pelvic obliquity and the ischial pressure injury, which healed completely. At the 1-year follow-up visit, there were no further signs of pressure injury. CONCLUSION: This case report describes transiliac-shortening osteotomy as a viable treatment option for non-healing ischial pressure injuries secondary to fixed pelvic obliquity.

Protocol for preclinical evaluation of locoregionally delivered CAR T cells in patient-derived xenograft models of brain tumors.

Here, we present a protocol for preclinical evaluation of locoregionally delivered CAR T cells in patient-derived xenograft models of primary, metastatic, and recurrent brain tumors. We provide instructions for isolating peripheral blood mononuclear cells (PBMCs), producing CAR T cells in conjunction with locoregional delivery, and preclinical trial design and analysis involving CAR T cells. Additionally, we describe comprehensive preclinical readouts and guidelines for critical endpoint sample collections. In line with clinical trial procedures, our protocol broadens available treatment modalities for direct clinical translation. For complete details on the use and execution of this protocol, please refer to Donovan et al.1.

Payload-delivering engineered γδ T cells display enhanced cytotoxicity, persistence, and efficacy in preclinical models of osteosarcoma.

T cell-based cancer immunotherapy has typically relied on membrane-bound cytotoxicity enhancers such as chimeric antigen receptors expressed in autologous αß T cells. These approaches are limited by tonic signaling of synthetic constructs and costs associated with manufacturing. γδ T cells are an emerging alternative for cellular therapy, having innate antitumor activity, potent antibody-dependent cellular cytotoxicity, and minimal alloreactivity. We present an immunotherapeutic platform technology built around the innate properties of the Vγ9Vδ2 T cell, harnessing specific characteristics of this cell type and offering an allocompatible cellular therapy that recruits bystander immunity. We engineered γδ T cells to secrete synthetic tumor-targeting opsonins in the form of an scFv-Fc fusion protein and a mitogenic IL-15Rα-IL-15 fusion protein (stIL15). Using GD2 as a model antigen, we show that GD2-specific opsonin-secreting Vγ9Vδ2 T cells (stIL15-OPS-γδ T cells) have enhanced cytotoxicity and promote bystander activity of other lymphoid and myeloid cells. Secretion of stIL-15 abrogated the need for exogenous cytokine supplementation and further mediated activation of bystander natural killer cells. Compared with unmodified γδ T cells, stIL15-OPS-γδ T cells exhibited superior in vivo control of subcutaneous tumors and persistence in the blood. Moreover, stIL15-OPS-γδ T cells were efficacious against patient-derived osteosarcomas in animal models and in vitro, where efficacy could be boosted with the addition of zoledronic acid. Together, the data identify stIL15-OPS-γδ T cells as a candidate allogeneic cell therapy platform combining direct cytolysis with bystander activation to promote tumor control.