Rapid Delivery Research Articles

Numerical analysis of launch process for a foldable quad-rotor UAV

Foldable quad-rotor UAV has the advantages of both artillery shells and rotor UAVs and can have the ability of long-distance rapid deployment and stagnation to perform tasks. To describe the rapid deployment process of gun-launched UAVs, a simplified internal ballistic and external ballistic modeling method is proposed. The ballistic parameters such as muzzle velocity, flight velocity variation, and flight trajectory are obtained. The effects of the variation of parameters such as initial pressure on the ballistic characteristics of the gun-launched UAV are analyzed. The research shows that the quad-rotor UAV can realize long-range rapid delivery and deployment after folding and pneumatic launching. With the increase of initial pressure, the muzzle velocity and range have a nonlinear increase. The related research results provide an important reference for the improvement of the subsequent gun-launched quad-rotor UAVs.

Service Time and Pricing Decisions in Online Retailing with Drop-Shipping and Guaranteed Service Framework

Many online retailers have adopted drop-shipping as their main order fulfillment strategy. Against this backdrop, this paper studies the service time and pricing decisions in an online retailing system in which the single retailer is served by either monopolistic or duopolistic suppliers. The suppliers are dominant in the Stackelberg game. We employ the guaranteed service framework to model the intricate relationship between service time and inventory. The model stipulates that the delivery of online orders must be completed within guaranteed service time. The equilibrium service times and prices are derived for both cases of monopolistic and duopolistic suppliers. In addition, we systematically analyze the impact of operational and market factors on service time, respectively, and rich insights have been obtained. Interestingly, we find that the presence of competition does not necessarily lead to more rapid delivery service. Suppliers in the duopoly market tend to adopt a price-based competitive strategy, i.e., they are better off by lowering price at the expense of longer service time, especially for the new entrant. However, as competition intensifies to some extent, suppliers are recommended to leverage on more responsive service to maintain or expand the customer base.

Highly Conductive Hierarchical TiO2 Micro‐Sheet Enables Thick Electrodes in Sodium Storage

AbstractTiO2‐based materials are considered to be the promising anodes of sodium‐ion batteries (NIBs) because of their high safety and good stability. However, their low specific capacity and high safety operating voltage plateau impose a severe challenge for high energy density batteries. Herein, interconnected micro‐sheets consisting of carbon nanotubes and sulfur doped TiO2 (CNT/S‐TiO2) are synthesized via an ultrasonic process and subsequent calcination, enabling the fabrication of high‐performance material. The utilization of SWCNT overcomes the structure instabilities during electrode preparation of thick electrodes. The incorporation of SWCNT and sulfur dopants in the CNT/S‐TiO2 composite not only enhances conductivity but also improves ion transport dynamics, resulting in rapid charge delivery and high specific capacity at the thick electrode level. Consequently, CNT/S‐TiO2 demonstrates excellent rate performance (from 0.3 to 15 C, with 72.4% capacity retention) and long cycling stability (10000 cycles at a load of 1.96 mg cm−2). More importantly, the high S‐TiO2 content (90%) in the thick electrode (21.2 mg cm−2) achieves a high areal capacity retention of 3.4 mA h cm−2 after 100 cycles, which surpasses the actual application requirements.

A five-day treatment course of zanamivir for the flu with a single, self-administered, painless microneedle array patch: Revolutionizing delivery of poorly membrane-permeable therapeutics

Seasonal influenza virus infections cause a substantial number of deaths each year. While zanamivir (ZAN) is efficacious against oseltamivir-resistant influenza strains, the efficacy of the drug is limited by its route of administration, oral inhalation. Herein, we present the development of a hydrogel-forming microneedle array (MA) in combination with ZAN reservoirs for treating seasonal influenza. The MA was fabricated from Gantrez® S-97 crosslinked with PEG 10,000. Various reservoir formulations included ZAN hydrate, ZAN hydrochloric acid (HCl), CarraDres™, gelatin, trehalose, and/or alginate. In vitro permeation studies with a lyophilized reservoir consisting of ZAN HCl, gelatin, and trehalose resulted in rapid and high delivery of up to 33 mg of ZAN across the skin with delivery efficiency of up to ≈75% by 24 h. Pharmacokinetics studies in rats and pigs demonstrated that a single administration of a MA in combination with a CarraDres™ ZAN HCl reservoir offered a simple and minimally invasive delivery of ZAN into the systemic circulation. In pigs, efficacious plasma and lung steady-state levels of ∼120 ng/mL were reached within 2 h and sustained between 50 and 250 ng/mL over 5 days. MA-enabled delivery of ZAN could enable a larger number of patients to be reached during an influenza outbreak.

Benchmarking halcyon ring delivery system for hypofractionated breast radiotherapy: Validation and clinical implementation of the fast-forward trial.

The aim of this study was to demonstrate the feasibility and efficacy of an iterative CBCT-guided breast radiotherapy with Fast-Forward trial of 26Gy in five fractions on a Halcyon Linac. This study quantifies Halcyon plan quality, treatment delivery accuracy and efficacy by comparison with those of clinical TrueBeam plans. Ten accelerated partial breast irradiation (APBI) patients (four right, six left) who underwent Fast-Forward trial at our institute on TrueBeam (6MV beam) were re-planned on Halcyon (6MV-FFF). Three site-specific partial coplanar VMAT arcs and an Acuros-based dose engine were used. For benchmarking, PTV coverage, organs-at-risk (OAR) doses, beam-on time, and quality assurance (QA) results were compared for both plans. The average PTV was 806 cc. Compared to TrueBeam plans, Halcyon provided highly conformal and homogeneous plans with similar mean PTVD95 (25.72 vs. 25.73Gy), both global maximum hotspot<110% (p=0.954) and similar mean GTV dose (27.04 vs. 26.80Gy, p=0.093). Halcyon provided lower volume of ipsilateral lung receiving 8Gy (6.34%vs. 8.18%, p=0.021), similar heart V1.5Gy (16.75%vs. 16.92%, p=0.872), V7Gy (0%vs. 0%), mean heart dose (0.96 vs. 0.9Gy, p=0.228), lower maximum dose to contralateral breast (3.2 vs. 3.6Gy, p=0.174), and nipple (19.6 vs. 20.1Gy, p=0.363). Compared to TrueBeam, Halcyon plans provided similar patient-specific QA pass rates and independent in-house Monte Carlo second check results of 99.6%vs. 97.9% (3%/2mm gamma criteria) and 98.6%versus 99.2%, respectively, suggesting similar treatment delivery accuracy. Halcyon provided shorter beam-on time (1.49 vs. 1.68min, p=0.036). Compared to the SBRT-dedicated TrueBeam, Halcyon VMAT plans provided similar plan quality and treatment delivery accuracy, yet potentially faster treatment via one-step patient setup and verification with no patient collision issues. Rapid delivery of daily APBI on Fast-Forward trial on Halcyon with door-to-door patient time<10min, could reduce intrafraction motion errors, and improve patient comfort and compliance. We have started treating APBI on Halcyon. Clinical follow-up results are warranted. We recommend Halcyon users consider implementing the protocol to remote and underserved APBI patients in Halcyon-only clinics.

Sequentially automated extraction of nucleic acids with magnetophoresis in microfluidic chips

A microfluidic platform is reported that utilizes magnetophoresis for the sequential and automated extraction of nucleic acid from biological samples. The system incorporates multiple microfluidic chips to process biological samples and extract nucleic acid using magnetic bead separation. The design is detailed, highlighting its efficiency and functionality. The injection pumps play a vital role in nucleic acid extraction by loading samples, cell lysis fluid, and magnetic nanoparticles into the microfluidic chips. These pumps enable the precise delivery of the required substances, allowing for efficient and effective extraction of nucleic acids. One embodiment of the microfluidic automated system provides a circuit design and implementation method. The programmable, fully automated system integrates various sensors and electronic components to enable efficient execution of the extraction process for multiple biomedical samples. The microfluidic system adopts a sequential automated process, enabling rapid delivery and minimizing the risk of sample contamination.

An observational study assessing the use of Sirolimus-eluting balloons for side-branch treatment in the provisional stenting of coronary bifurcations

BackgroundDrug eluting balloons (DEB) are a feasible method of rapid delivery of drug to a coronary vessel wall. Their efficacy has been established for the treatment of in-stent restenosis and small vessel disease but there is limited data for their use in bifurcation lesions. ObjectiveThe aim of this study was to assess the effectiveness of provisional upfront side-branch DEB use in bifurcation lesions compared to a simple balloon (POBA) or upfront 2 stent bifurcation strategy. MethodsWe conducted an observational study of 625 patients undergoing PCI to bifurcation lesions. All the patients had a DES deployed in the main vessel (MV). Decision on revascularization option for the side branch (SB) was made by the operator. The primary endpoint was target vessel failure. Secondary endpoints were target vessel myocardial infarction and all-cause mortality. Results311 patients had upfront DEB to the SB whilst the remaining were treated with either DES (188) or POBA (126). Baseline characteristics were similar aside from history of previous MI, which were higher in patients treated with DES or POBA, p = 0.009 whereas patients with previous CABG were likely to undergo DEB treatment (p = 0.004). TVF was more likely to occur in the POBA group (7.5 %) compared to the DEB (3.3 %) and DES (3.3 %) groups (p = 0.0019). There was no significant difference in TV-MI (p = 0.62) or death (p = 0.98) between the groups. ConclusionThis study suggests that provisional bifurcation stenting with upfront Sirolimus DEB use in the SB is an effective treatment for non-LMS bifurcation PCI.

Design of embedded software architecture for spacecraft electric propulsion system

With the rapid growth of the number of spacecraft tasks and the complexity of the system, spacecraft software development is faced with the challenges of high-quality and rapid delivery, increased complexity, and frequent changes in requirements. The reuse rate of software assets needs to be improved urgently. In order to realize cross-platform and cross-project reuse of software design, this paper studies the design of electric propulsion software architecture. Carry out requirements decomposition and subsystem division of electric propulsion systems for different platforms, extract common requirements and variability requirements at the system level and subsystem level based on the Feature-Oriented Domain Analysis method, and establish a requirements model. Based on the requirements model, an electric propulsion software architecture integrating “event-driven + components” is proposed, and the classic event-driven model of “publish-subscribe” is adaptively improved. The architecture has been instantiated and applied to 16 projects on 4 platforms, and the reuse rate of core assets has reached 70%. This paper has certain guidance and reference significance for spacecraft software asset reuse and platform construction.

An Engineered Nanosugar Enables Rapid and Sustained Glucose‐Responsive Insulin Delivery in Diabetic Mice (Adv. Mater. 21/2023)

Insulin Delivery In article number 2210392, Christoph E. Hagemeyer, Francesca Cavalieri, and co-workers report how biodegradable and charge-switchable phytoglycogen nanoparticles with glucose-sensitive phenylboronic acid groups and amine moieties can be engineered to form nanocomplexes with insulin for its rapid and efficient glucose-responsive delivery. Subcutaneous injection of nanocomplexes in two distinct diabetic mouse models helps to maintain normal glucose levels for up to 13 h.

Immediate Medical Care Rendered by U.S. Law Enforcement Officers After Officer-Involved Shootings – An Open-Access Public Domain Video Analysis

Introduction:After officer-involved shootings, rapid delivery of emergency medical care is critical but may be delayed due to scene safety concerns. The purpose of this study was to describe medical care rendered by law enforcement officers (LEO) after lethal force incidents.Method:Retrospective analysis of open-source video footage of officer-involved shootings (OIS) occurring between 2/15/2013 and 12/31/2020. Frequency and nature of care provided, time until LEO and emergency medical services (EMS) care, and mortality outcomes were evaluated. The study was deemed exempt by the Mayo Clinic Institutional Review Board.Results:342 videos were included in the final analysis. LEOs rendered care in 172 (50.3%) incidents. The average elapsed time from the time of injury to LEO-provided care was 155.8 + 198.8 seconds. Hemorrhage control was the most common intervention performed. An average of 214.2 seconds elapsed between LEO care and EMS arrival. No mortality difference was identified between LEO vs EMS care (p = 0.1631). Subjects with truncal wounds were more likely to die than those with extremity wounds (p &lt; 0.00001).Conclusion:LEO rendered medical care in half of all OIS incidents, initiating care on average 3.5 minutes prior to EMS arrival. Although no significant mortality difference was noted for LEO versus EMS care, this finding must be interpreted cautiously, as specific interventions, such as extremity hemorrhage control, may have impacted select patients. Future studies are needed to determine optimal LEO care for these patients.

Shape-stabilized 1-hexadecanol/g-C3N4/Cu composite phase change material with high thermal conductivity for efficient photo-thermal conversion

Phase change materials (PCM) have received much attention for thermal energy storage and release in the form of latent heat. 1-hexadecanol (HD), as a representative of organic phase change materials, has the advantages of high thermal storage density, almost constant operating temperature and stable thermochemical properties, which shows outstanding potential in the field of phase change energy storage. Nevertheless, single HD as thermal storage material inevitably faces challenges in terms of liquid phase leakage, low thermal conductivity, and poor photo-thermal conversion. To further improve the practical application of HD, we demonstrate a convenient encapsulation and modification strategy of composite phase change materials (CPCMs) with low liquid leakage and high thermal conductivity. Hence, a novel shape-stabilized Cu-doped HD/ graphitic carbon nitride (g-C3N4) CPCM was developed for efficient photo-thermal storage. By the melt blending method, HD is infiltrated into tightly stacked and aligned nano-porous g-C3N4, and the carbon-based lattice inlay achieves the encapsulation of HD to solve the leakage problem during the solid–liquid phase transition. Then, metallic Cu powder is introduced to further strengthen the thermal conductivity of the materials. With this encapsulation and modification strategy, the obtained 5 wt% Cu-doped HD/g-C3N4 composites (CPCM3) exhibits superior performance in both thermal and optical energy storage. This composite has appropriate phase change temperature and extremely high heat storage density, with melting temperature and latent heat of 48.88 °C and 249.63 J/g. The corresponding solidification temperature and latent heat is 48.52 °C and 242.22 J/g, respectively. Its thermal conductivity is enhanced to 0.5307 W/m·K, which is 59.8% higher than pure HD. The photo-thermal conversion efficiency is up to 81.6% for rapid solar energy harvesting and delivery. In particular, after 100 times thermal cycling tests and thermogravimetric analysis, this special CPCM can maintain good thermal reliability and thermal stability. In conclusion, the composite phase change materials obtained by the synergistic modification strategy of nano-porous g-C3N4 and metallic Cu significantly improved the thermochemical properties of HD. This work provides a practical and efficient synthetic strategy for the preparation of CPCMs, which is expected to present a promising future in the field of solar conversion and storage.

Interim Analysis of Subject Impression Data for STS101 From the Phase 3 Open-Label ASCEND Study (P13-12.003)

Interim Analysis of Subject Impression Data for STS101 From the Phase 3 Open-Label ASCEND Study (P13-12.003)

Interim Analysis of STS101 Nasal Safety Data From the Phase 3 Open-Label ASCEND Migraine Study (P13-12.006)

<h3>Objective:</h3> To assess the long-term nasal safety and tolerability of STS101 in the acute treatment of migraine. <h3>Background:</h3> STS101 (dihydroergotamine nasal powder) is a novel investigational product with rapid and easy nasal delivery. The ASCEND study assesses the safety and tolerability of STS101 5.2 mg in the acute treatment of migraine with/without aura over 12 months. <h3>Design/Methods:</h3> ASCEND (NCT04406649) is a multi-center, multiple-dose, open-label study in adults (18–65 years) with migraine. Participants self-administered STS101 for ≤2 doses/24 hours and ≤12 doses/month for acute treatment of migraines for 12 months. This interim analysis included participants exclusively using the STS101 incorporating the second-generation nasal delivery device planned for commercialization. Nasal safety assessments included nasal treatment-emergent adverse events (TEAEs), subjective assessments of nasal irritation, and a smell test (SIT). Objective nasal assessments were done by trained study personnel on a 4-point severity scale to document nasal erythema, edema, rhinorrhea, bleeding, and nasal mucosa ulcerations. <h3>Results:</h3> This population included 344 subjects who treated 5,571 attacks with 6,918 doses of STS101 and was 40.4±10.9 years old (mean±SD), 85.8% female, and 87.5% Caucasian. Overall, 97 subjects (28.2%) reported nasal/local TEAEs; 8 of 344 subjects (2.9%) discontinued the study due to nasal/local TEAEs including nasal burning/discomfort (5), nasal bleeding (1), rhinitis (1), and throat tightness (1). Most frequently reported nasal/local related TEAEs were nasal discomfort (38 [11.0%] subjects; 338 [6.1%] attacks), dysgeusia (26 [7.6%]; 154 [2.8%]), and nasal congestion (14 [4.4%]; 198 [3.6%]). At 12 months, 99.5%, 95.4%, 93.5%, and 94.4% of subjects had no nasal bleeding/ulceration, edema, erythema, or rhinorrhea, respectively. No clinically relevant findings were seen from nasal examinations, subjective nasal irritation assessments, or smell tests. <h3>Conclusions:</h3> Nasal safety data from 5,571 treated attacks demonstrate the safety and tolerability of STS101 for the acute treatment of migraine. <b>Disclosure:</b> Dr. Spierings has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Manistee. Dr. Spierings has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Lundbeck. Dr. Spierings has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Lilly. Dr. Spierings has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Abbvie. Detlef Albrecht has received personal compensation for serving as an employee of Satsuma. Detlef Albrecht has stock in Satsuma. Dr. Rapoport has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for AbbVie, Amgen, Biohaven, Cala Health, Satsuma, Teva Pharmaceutical Industries, Theranica, Xoc and Zosano. Dr. Rapoport has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for AbbVie, Amgen, Biohaven, Lundbeck and Teva Pharmaceutical Industries. Dr. Rapoport has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Neurology Reviews.

Interim Analysis of Long-Term Safety and Tolerability Data of STS101 From the Phase 3 Open-Label ASCEND Study (P13-12.004)

Interim Analysis of Long-Term Safety and Tolerability Data of STS101 From the Phase 3 Open-Label ASCEND Study (P13-12.004)

How to do Advice and Guidance well.

The COVID-19 pandemic has accelerated a rapid expansion of digital Advice and Guidance (A&G) across UK medical and surgical specialties. Dermatology A&G requests have increased by over 400% since the onset of the pandemic in 2020, with rapid expansion of teledermatology A&G services across England. Dermatology A&G is usually carried out asynchronously through dedicated digital platforms such as the NHS e-Referral service, with streamlined conversion to referral if clinically indicated. A&G with images is advocated as the main referral pathway to dermatology specialist services in England (excluding the two-week wait suspected skin cancer pathway). Providing dermatological care through A&G requires specific clinical skill sets to ensure rapid, safe and collaborative delivery, and optimisation of educational benefit. Little published guidance is available to signpost clinicians to what constitutes a high-quality A&G request and response. This educational article discusses good clinical practice based on extensive local and national experience from primary and secondary care doctors. We cover digital communication skills, shared decision making, clinical competency, and building collaborative links between patients, referrers and specialists. High quality A&G, with agreed turn-around times and optimisation of technology can significantly streamline patient care and strengthen links between clinicians, providing it is appropriately resourced within the wider planning of elective care and outpatient activity.

Reducing the time delay of oxygen transport to the neonate on continuous positive airway pressure support: A bench study.

Premature newborns often require oxygen support as part of their therapy. Systems for oxygen administration are developed to assure adequate oxygenation of newborns. Several factors were identified in the systems that contribute to the time delay between the change in the set inspiratory oxygen fraction and its actual delivery to tissues. In this study, we aimed to reduce the physical delay in oxygen delivery to newborns. We developed an O2 Flush System (O2-FS) that brings the source of oxygen as close to a patient as possible to make oxygen available for rapid delivery that compensates for the physical delay in the ventilator circuit. The O2-FS system is built around an electromechanical on/off valve. We validated the O2-FS concept in experiments with non-invasive Continuous Positive Airways Pressure (CPAP) ventilators. The O2-FS accelerated oxygen delivery with all the tested systems and arrangements, typically by 5-15 s. We also observed that the application of supplemental oxygen increased the pressure in the ventilator circuit by 3-4 cmH2O which may mitigate the apneic pauses that are common in premature newborns. The O2-FS system may work as a universal accessory of the CPAP lung ventilator and shorten the distribution of oxygen to the patient during oxygen desaturation events, possibly eliminating or interrupting apneic pauses in neonates, for whom oxygen therapy is an essential treatment. In clinical practice, the O2-FS could help maintain normoxemic saturation values through adequate oxygen dosing in preterm neonates, thus reducing morbidity and mortality.

Biodegradable Microneedles Array with Dual-Release Behavior and Parameter Optimization by Finite Element Analysis

Microneedles (MNs) are particularly attractive for transdermal administration because of the improved safety, patient compliance and convenience. Dissolving MNs could provide rapid transdermal delivery, but with relatively low mechanical strength and almost no sustainability. On the other hand, hydrogel MNs are complicated to fabricate and have risk concerns. Herein, we developed a biodegradable MNs array composed of biocompatible silk fibroin and poly(vinyl alcohol) to overcome these limitations. Finite element analysis was employed for parameter optimization. The MNs array fabricated by the optimal parameters and material displayed sufficient mechanical strength to disrupt stratum corneum and formed microchannels for transdermal delivery. Dual-release profile was observed in the MNs array, with rapid release in the beginning, and prolonged release afterward. This release behavior fits Weibull release model and is favorable for topical application. The initial immediate release can quickly deliver active compounds to reach the therapeutic effective concentration and facilitate skin penetration, and the sustained release may supply the skin with active compounds over a prolonged period. This biodegradable MNs array is easy to fabricate, mechanically robust, could eliminate safety concerns, and provide the sustainability and advantage for large-scale production.

Best Practices for Implementation of an Employee Health COVID-19 Vaccine Clinic-A Model for Future Pandemic Preparedness.

The aims of the study are to determine best practices from two large-scale, academic medical centers' employee coronavirus 2019 (COVID-19) vaccination clinics and to apply them to create scalable modules for rapid administration of 10,000 vaccinations. The weekly number of COVID-19 vaccine doses administered was captured. Processes were compared to determine best practices, which informed the scalable financial model. Within the first 3 months, more than 60,000 COVID-19 vaccine doses were administered, and 70% of employees were fully vaccinated in 4 months with more than 95% by the vaccine mandate deadline. The estimated cost of delivering one dose was $29.95 ($299,505/10,000) compared with $35-$39 per dose when delivered by an on-site retail pharmacy. Successful, safe, and rapid delivery of more than 60,000 COVID-19 vaccine doses in 3 months is practical and scalable. Learnings go beyond COVID-19 and can be applied to future outbreaks/pandemics.

Design of medical tympanostomy conduits with selective fluid transport properties.

Implantable tubes, shunts, and other medical conduits are crucial for treating a wide range of conditions from ears and eyes to brain and liver but often impose serious risks of device infection, obstruction, migration, unreliable function, and tissue damage. Efforts to alleviate these complications remain at an impasse because of fundamentally conflicting design requirements: Millimeter-scale size is required to minimize invasiveness but exacerbates occlusion and malfunction. Here, we present a rational design strategy that reconciles these trade-offs in an implantable tube that is even smaller than the current standard of care. Using tympanostomy tubes (ear tubes) as an exemplary case, we developed an iterative screening algorithm and show how unique curved lumen geometries of the liquid-infused conduit can be designed to co-optimize drug delivery, effusion drainage, water resistance, and biocontamination/ingrowth prevention in a single subcapillary-length-scale device. Through extensive in vitro studies, we demonstrate that the engineered tubes enabled selective uni- and bidirectional fluid transport; nearly eliminated adhesion and growth of common pathogenic bacteria, blood, and cells; and prevented tissue ingrowth. The engineered tubes also enabled complete eardrum healing and hearing preservation and exhibited more efficient and rapid antibiotic delivery to the middle ear in healthy chinchillas compared with current tympanostomy tubes, without resulting in ototoxicity at up to 24 weeks. The design principle and optimization algorithm presented here may enable tubes to be customized for a wide range of patient needs.

Abstract 540: c-MET mutations sensitize to antibody-drug conjugate telisotuzumab vedotin through efficient internalization and rapid intracellular drug delivery

Abstract Background: Telisotuzumab vedotin (Teliso-V) is an antibody-drug conjugate (ADC) composed of the c-MET antibody ABT-700 and the microtubule inhibitor monomethyl auristatin E (MMAE). Patients with EGFR wildtype (WT) nonsquamous non-small cell lung cancer with high c-MET expression had an overall response rate of 54% with Teliso-V. In addition to overexpression and amplification, genetic alterations in c-MET, such as exon 14 deletion (ex14del) and missense mutations in the tyrosine kinase domain (TKD), contribute to its constitutive activation. The efficacy of Teliso-V in context of these genomic backgrounds is currently unknown. Methods: Recombinant retroviruses were used to express WT-c-MET, c-MET-TKD (D1228H/V/N and Y1230C/H mutations), c-MET-Y1003F/N (CBL E3 ubiquitin ligase binding site mutation), and c-MET-ex14del (47 aa juxtamembrane deletion) mutants in NIH3T3 and Ba/F3 cells. c-MET surface expression, intracellular signaling, ADC internalization and endolysosomal (EL) trafficking (using pHrodo Red-labeled Teliso-V), intracellular MMAE by LC/MS, and Teliso-V sensitivity were studied in 2D/3D cell cultures. Full-length c-MET protein structures were created with the ColabFold program and molecular dynamics simulation software (with/without artificial lipid bilayer) was used to predict the mechanistic basis for differential function. Results: c-MET expression was required for Teliso-V cytotoxicity and intracellular payload delivery in all cell lines. Compared with WT-c-MET, various mutants showed oncogene-driven transformation evident by elevated levels of phosphorylated c-MET/AKT, cytokine-independent colony formation, oncogene-driven proliferation, and tyrosine kinase inhibitor (TKI) resistance. Interestingly, c-MET-TKD-expressing cells were the most sensitive to Teliso-V, which was associated with faster ADC internalization and EL trafficking. An AI-generated protein model and associated molecular dynamics simulation demonstrated that all oncogenic TKD variants tested stabilized the c-MET-plexin-semaphorin-integrin domain (R592-L614), known for its ability to position the extracellular ligand-binding (ELB) site for optimal activation. Conclusions: c-MET-TKD mutations induced TKI resistance and enhanced MMAE delivery in association with robust ADC internalization and EL trafficking. Previous studies have shown that the HER2 ADC fam-trastuzumab deruxtecan-nxki was highly effective in cell lines and patients with ERBB2 kinase domain-mutant lung cancer via a similar mechanism, raising the possibility that this may be a general phenomenon across receptor tyrosine kinase-targeting ADCs. c-MET-TKD mutations are predicted to stabilize the ELB conformation to activate enhanced oncogenic signaling that may contribute to rapid endocytosis-mediated drug delivery. Citation Format: Izhar S. Batth, Bijay S. Jaiswal, Dolonchampa Maji, Robert Sparks, William Glauser, Tamar Uziel, D. Ross Camidge, Athan Vasilopoulos, Peter Ansell, PK Epling-Burnette. c-MET mutations sensitize to antibody-drug conjugate telisotuzumab vedotin through efficient internalization and rapid intracellular drug delivery [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 540.