Check Point Research Articles

Check(point) yourself before you wreck yourself in tumors.

Check(point) yourself before you wreck yourself in tumors.

Target Therapy vs the Immune Check Point Inhibitors in Lung Cancer: Costs and Caps Platform

The immune check point inhibitors (ICI) and target therapy (TT) Osimertinib (Osi) prolonged survival in advanced/metastatic non-small cell lung cancer (a/m-NSCLC). Costs of ICI were previously investigated (ESMED, July 2022) while TT being overlooked. In 2022, insulin monthly cost was capped at $35 for Medicare patients. We aimed to 1- Attach a $ amount to results of the major relevant TT and ICI clinical studies and weigh their relative costs 2- Reason that utilization threshold caps are necessary to contain cost of extended therapy Methods: In this prospective observational study, annual costs of the approved and widely used TT were calculated as the monthly optimal dose x 12. Costs of the 5-approved ICI in 1-st-line a/m NSCLC were calculated as mg/m2 or per 80 kg x price x number of cycles. Results: Median annual 5-TT cost was $228,000 vs 5-ICI of $134,786 at 1.69 ratio. At 10%, estimated coverage of pharmacy and nursing costs, ratio dropped to 1.52. The 1-3-year Osi costs were $248,372-$745,116, Crizotinib $226,308 -$678,924 and Larotrectinib $399,372-$1,198,116. Pembrolizumab were $134,796-$404,388, Atezolizumab $124,761-$374,283 and Cemiplimab $125,108-$375,324. Applying $500,000 caps, the ICI 3-year costs were all below threshold. TT medium 3-year cost was $684,000, exceeding cap by $184,000, Osi by $245,116 and Crizotinib by $178,924. Larotrectinib 2-3-year costs were higher by $298,744 - $698,116. We reasoned that if 1,000 US patients treated with TT at the annual median, cost mounts to $684,000,000. In Europe, 2,000 patients’ cost would be $1,368,000,000. Conclusions: The median TT/ICI was more costly at 1.52 ratio. Drug costs were determined by the number of re-purchases, the 1st-buy, if followed, was considered a down payment. Cap implementations are necessary to contain costs of extended therapy.

A Post-Mortem Analysis of the Tax Appeal Tribunal's Decision in Check Point Software Technologies B.V. Nigeria Limited v FIRS: Re-stressing the Domestication of Treaty Requirement Under the Nigerian Constitution

A Post-Mortem Analysis of the Tax Appeal Tribunal's Decision in Check Point Software Technologies B.V. Nigeria Limited v FIRS: Re-stressing the Domestication of Treaty Requirement Under the Nigerian Constitution

Immune checkpoint inhibitors for RET fusion non-small cell lung cancer: hopes and challenges.

Immune ch eckpoint inhibitors (ICIs) represent a milestone in advanced nonsmall cell lung cancer (NSCLC). Nevertheless, NSCLC with known oncogenic drivers has been overlooked in most studies evaluating anti-programmed death-1/programmed death ligand 1. Rearranged during transfection proto-oncogene (RET) gene fusion was identified in 1-2% of NSCLC patients. More recently, two selective RET inhibitors, selpercatinib and pralsetinib, demonstrated higher efficacy and good tolerability. In contrast, the activity of ICIs in RET fusion NSCLC has not been well characterized. Here, we analyzed the clinical data of ICIs and discussed the suitable time to introduce ICIs in RET fusion NSCLC. Finally, we put forward future strategies to adequately maximize the efficacy of ICIs treatment in patients with RET fusion NSCLC in the upcoming era of combination immunotherapies.

PENGARUH KUALITAS PELAYANAN PETUGAS AVSEC DI SECURITY CHECK POINT (SCP) TERHADAP KEPUASAN PENUMPANG DI BANDAR UDARA SULTAN BABULLAH TERNATE

Aviation Security (AVSEC) is a work unit formed by PT. Angkasa Pura in fulfilling international and national regulations as a manager and provider of airport security services must have the required license according to the position. The quality of security services provided by security officers or Aviation Security (AVSEC) at the Security Check Point (SCP) unit at Sultan Babullah Airport Ternate is very important for passengers. the researcher got information from seniors who had already carried out On Job Training (OJT) where there were some passengers who complained about the service during the inspection. Therefore, the researcher aims to find out whether there is an influence on the quality of service of avsec officers at the security check point on passenger satisfaction and also to find out how much influence the quality of service of avsec officers at the security check point has on passenger satisfaction at Sultan Babullah Airport, Ternate
 This study uses quantitative data. The data used in this study were taken from primary data based on questionnaires distributed to passengers at Sultan Babullah Airport Ternate for the period February 2022. With a total of 96 people, the data analysis technique used was simple linear regression analysis, T test, coefficient of determination and normality test.
 The results showed that Ho was rejected and Ha was accepted, which means that there is an influence of service quality for Avsec Officers at Security Check Point (SCP) on Passenger Satisfaction at Sultan Babullah Airport, Ternate. The T test results show tcount = 15.212> ttable value = 1.985. The results of the Coefficient of Determination test which show how much influence the service quality variable (X) has on the passenger satisfaction variable (Y) it is known that the determination coefficient value is 71.1%, which means that the service quality variable (X) contributes 71.1% to the passenger satisfaction variable. (Y), while the remaining 28.9% was caused by other factors not examined by the researcher.
 Keywords: Quality of Service, Passenger Satisfaction, Sultan Babullah Ternate

Evaluating the Influence of Data Entropy in the Use of a Smart Equipment for Traffic Management at Border Check Point

The transit through a Border Check Point of cargo vehicles supposes, in the case of the Romanian highway network, the carrying out of a process of weighing and verifying of transport licenses. The limited number of weighing equipment and the long duration of these processes cause large queues and long waiting times. A solution for these problems is to use smart equipment to identify the cargo vehicles and to separate the vehicles that require weighing from exempted ones. The separation process is made using external input data. The quality of received data can generate some dysfunctionality in the separation process. The discrete simulation model can be used to evaluate the influence of the uncertainty over the system serving parameters. A study case is developed for a real situation using real data collected from a Romanian Highway Traffic Control Center (HTMC). The results are used in the implementation of the new smart equipment in a Romanian Border Check Point.

S2945 Check Point SOS! A Case of Cemiplimab-Associated Sinusoidal Obstruction Syndrome

Introduction: Hepatic veno-occlusive disease (VOD) or sinusoidal obstruction syndrome (SOS), is a clinical syndrome characterized by hepatomegaly, right-upper quadrant pain, and ascites that occurs most commonly in the setting of high-dose chemotherapy or hematopoietic stem cell transplantation (HSCT). The diagnosis can be confirmed on biopsy. Cemiplimab is an immune checkpoint inhibitor recently approved for the treatment of cutaneous squamous cell carcinoma. There are currently no known reports of immune checkpoint inhibitor-related VOD/SOS. Case Description/Methods: A 58-year-old female with a history of locally advanced basal cell carcinoma of the left eye treated with six months of Cemipilimab presented with ascites. On admission, labs were notable for a total bilirubin of 1.2, mildly elevated liver function tests, alkaline phosphatase 884, and international normalized ratio 2.1. A diagnostic tap revealed a high SAAG ascites that was negative for infection. A comprehensive serological workup for viral, metabolic and autoimmune causes was unrevealing. A transjugular liver biopsy demonstrated a hepatic venous pressure gradient of 18mmHg, nodular regenerative hyperplasia (NRH), and portal venopathy. The patient was discharged on steroids but returned one month later for recurrent ascites and worsening bilirubin to 12.6 (direct 7.3); COVID PCR was negative. A full rheumatologic and vasculitis workup was unremarkable. Repeat biopsy (Figure 1) demonstrated moderate NRH changes, prominent central vein sclerosis with fibrous obliteration, signs of SOS/VOD and central venulitis with fibrotic changes with sinusoidal portal hypertension. Discussion: VOD occurs most often with hematopoietic stem cell transplantation, and chemotherapeutic agents. Here we present the first case of checkpoint inhibitor-induced VOD/SOS. Despite discontinuation of the offending agent and a trial of steroids, the patient’s clinical course continued to deteriorate. She eventually developed refractory ascites and portosystemic encephalopathy. She was deemed not a candidate for liver transplant given her underlying malignancy. She was transitioned to home hospice before further treatment, such as Defibrotide could have been pursued. VOD associated with immune checkpoint inhibition should be considered in the differential of patients who develop new onset liver dysfunction and ascites while receiving these medications.Figure 1.: Sinusoidal dilatation and congestion alongside central vein sclerosis. These are common findings of sinusoidal obstruction syndrome on liver biopsy.

CD8+ and FoxP3+ T-Cell Cellular Density and Spatial Distribution After Programmed Death-Ligand 1 Check Point Inhibition.

To analyze CD8+ and FoxP3+ T-cell cellular density (CD) and intercellular distances (ID) in head and neck squamous cell carcinoma (HNSCC) samples from a neoadjuvant trial of durvalumab +/- metformin. Paired pre- and post-treatment primary HNSCC tumor samples were stained for CD8+ and FoxP3+. Digital image analysis was used to determine estimated mean CD8+ and FoxP3+ CDs and CD8+-FoxP3+ IDs in the leading tumor edge (LTE) and tumor adjacent stroma (TAS) stratified by treatment arm, human papillomavirus (HPV) status, and pathologic treatment response. A subset of samples was characterized for T-cell related signatures using digital spatial genomic profiling. Post-treatment analysis revealed a significant decrease in FoxP3+ CD and an increase in CD8+ CDs in the TAS between patients receiving durvalumab and metformin versus durvlaumab alone. Both treatment arms demonstrated significant post-treatment increases in ID. Although HPV+ and HPV- had similar immune cell CDs in the tumor microenvironment, HPV+ pre-treatment samples had 1.60 times greater ID compared with HPV- samples, trending toward significance (p= 0.05). At baseline, pathologic responders demonstrated a 1.16-fold greater CD8+ CDs in the LTE (p= 0.045) and 2.28-fold greater ID (p= 0.001) than non-responders. Digital spatial profiling revealed upregulation of FoxP3+ and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) in the TAS (p= 0.006, p= 0.026) in samples from pathologic responders. Analysis of CD8+ and FoxP3+ detected population differences according to HPV status, pathologic response, and treatment. Greater CD8+-FoxP3+ ID was associated with pathologic response. CD8+ and FoxP3+ T-cell distributions may be predictive of response to immune checkpoint inhibition. gov (Identifier NCT03618654). 3 Laryngoscope, 133:1875-1884, 2023.

Integrative Expression, Survival Analysis and Cellular miR-2909 Molecular Interplay in MRN Complex Check Point Sensor Genes (MRN-CSG) Involved in Breast Cancer

BackgroundBreast cancer, an emerging global challenge, is evidenced by recent studies of miRNAs involvement in DNA repair gene variants (MRE11, RAD50, and NBN as checkpoint sensor genes (CSG) – MRN-CSG). The identification of various mutations in MRN-CSG and their interactions with miRNAs is still not understood. The emerging studies of miR-2909 involvement in other cancers led us to explore its role as molecular mechanistic marker in breast cancer. Materials and MethodsThe genomic and proteomic data of MRN-CSG of breast cancer patients (8426 samples) was evaluated to identify the mutation types linked with the patient's survival rate. Additionally, molecular, 3D-structural and functional analysis was performed to identify miR-2909 as regulator of MRN-CSG. ResultsThe genomic and proteomic data analysis shows genetic alterations with majority of missense mutations [RAD50 (0.7%), MRE11 (1.5%), and NBN (11%)], though with highest MRE11 mRNA expression in invasive ductal breast carcinoma as compared to other breast cancer types. The Kaplan–Meier survival curves suggest higher survival rate for unaltered groups as compared to the altered group. Network analysis and disease association of miR-2909 and MRN-CSG shows strong interactions with other partners. The molecular hybridization between miR-2909-RAD50 and miR-2909-MRE11 complexes showed thermodynamically stable structures. Further, argonaute protein, involved in RNA silencing, docking studies with miR-MRE11-mRNA and miR-RAD50-mRNA hybridized complexes showed strong binding affinity. ConclusionThe results suggest that miR-2909 forms strong thermodynamically stable molecular hybridized complexes with MRE11 and RAD50 mRNAs which further strongly interacts with argonaute protein to show potential molecular mechanistic role in breast cancer.

Analisis Penerapan Prosedur Penanganan Barang Berbahaya di Security Check Point (SCP) 1 Bandar Udara Internasional Raja Haji Fisabilillah Tanjungpinang

The implementation of procedures in dealing with dangerous goods in accordance with the existing rules in Security Check Point (SCP) 1 is one of the first steps in improving security at the airport, considering the increasingly diverse ways to commit crimes found at the airport related to the inspection of passengers and luggage. The purpose of this study is to analyze the implementation of hazardous goods handling procedures at Security Check Point (SCP) 1 and to find out the constraints of Aviation Security officers in handling dangerous goods at Security Check Point (SCP) 1 Raja Haji Fisabilillah Tanjungpinang International Airport.
 This study uses a descriptive qualitative approach with data collection techniques using participant observations, structured interviews, and documentation collected from related sources and when the author goes down the field.
 The results of this study show that the implementation of hazardous goods handling procedures at Security Check Point (SCP) 1 has been implemented in accordance with the rules or Standard Operating Procedures by Aviation Security personnel of Raja Haji Fisabilillah International Airport. This application is not only done when there are instructions from the x-ray operator but can also be applied if it looks suspicious passenger movements. In addition, there are also obstacles, namely differences of opinion with passengers who are arrogant and do not understand the regulations regarding luggage inspection which belongs to the category of dangerous goods or prohibited items and facilities that are suddenly error or not primed when used or run during the inspection time.
 Keywords : Aviation Security, Security Check Point (SCP) 1, application of procedures for handling dangerous goods.

847P Precision oncology for resistant acral, mucosal and cutaneous melanomas: A prospective broad high throughput genomics feasibility study

There are limited therapies for metastatic cutaneous, mucosal and acral melanomas (m) progressing after checkpoint (CPI) and BRAF/MEK (TKI) inhibitors. The Treat20 Plus study aimed to identify oncogenic drivers through high throughput genomics that could inform treatment recommendations ((Trec). From 1.2016 - 1.2019, 54 resistant m were prospectively subjected to a comprehensive molecular analysis (WGS, WES, RNA seq), that allowed a molecular tumor board to make individualized treatment recommendations. Primary sites: cutaneous (34), mucosal (16), acral (4), PS 1(0-3), abnormal LDH (37), # of therapies 5(2-22) (surgery 2(0-18), irradiation 1 (0-5), CPI 2(1-5), TKI 0 (0-2), chemo 0(0-2). No Trec in 10 p (low purity 7, early PD 3). Trec in 44 p (81%) with 4 (0-5) / p, for a total of 108 Trec including inhibitors of MEK 27%, CDK4/6 23%, TKI 7%, MET 6%, MTOR 6%, EGFR, FGFR, RAS 5 %, ALK 4%, NOTCH and PARP 2%, IGFR, NTRK, IDO and ER 1%. Treatment realization made in 21/44 p (48 %). Non-realization was early PD (14), still on CPI (6), on chemo (1), no druggable mutation (2). Among the 21 treated p 1 CR, 4 PR (RR: 24 %; 9 % of whole cohort (wc)), 3 SD (Clinical benefit: 38 %; 15% of wc) and 13 PD. Duration of the clinical benefit ranged from 147-678+ d. Resistance to prior TKI were observed in 8/9 BRAF V600E p by BRAF fusion (1), splicing (1), NRAS mutation (4), PTEN (2), RB1 (1), CDKN2A loss (2). CPI resistance mutations were shown in B2M (1), SOCS1 (1), MDM2 (1) and MDM2 focal amplification (2), and homozygous deletion in PTEN (4), but no relevant JAK1, JAK2, IRF1, IFNGR1/2, PIAS4, EGFR, MDM4, EZH2 alterations. Responding p had BRAF 599delinsTT (1), BRAF G469S (1), cKIT (2) mutations and NTRK fusion (1). Stabilization: IGFR (1) MET overexpression (1), CDKN2A loss (1). Among the seven p without BRAF V600E, NRAS and NF1 mutation (triple-negative profile) six had a clinical benefit. PFS for the treated p: 2.26 months (95%CI: 0.00-4.98) and the OS for the 54 p: 8.7 months (95 % CI: 1.56-15.97). For resistant acral, mucosal and cutaneous m, precision oncology was feasible with Trec in 81 % of p. It uncovered targetable alterations that led to a clinical benefit in 38 % of p mainly presenting with absence of BRAF V600E, NRAS and NF1 mutation.

Analisis Penerapan Prosedur Penanganan B3 di Bandar Udara Internasional Raja Haji Fisabilillah Tanjungpinang Riau

The implementation of procedures in dealing with dangerous goods in accordance with the existing rules in Security Check Point (SCP) 1 is one of the first steps in improving security at the airport, considering the increasingly diverse ways to commit crimes found at the airport related to the inspection of passengers and luggage. The purpose of this study is to analyze the implementation of hazardous goods handling procedures at Security Check Point (SCP) 1 and to find out the constraints of Aviation Security officers in handling dangerous goods at Security Check Point (SCP) 1 Raja Haji Fisabilillah Tanjungpinang International Airport. This study uses a descriptive qualitative approach with data collection techniques using participant observations, structured interviews, and documentation collected from related sources and when the author goes down the field.The results of this study show that the implementation of hazardous goods handling procedures at Security Check Point (SCP) 1 has been implemented in accordance with the rules or Standard Operating Procedures by Aviation Security personnel of Raja Haji Fisabilillah International Airport. This application is not only done when there are instructions from the x-ray operator but can also be applied if it looks suspicious passenger movements. In addition, there are also obstacles, namely differences of opinion with passengers who are arrogant and do not understand the regulations regarding luggage inspection which belongs to the category of dangerous goods or prohibited items and facilities that are suddenly error or not primed when used or run during the inspection time.
 Keywords : Aviation Security, Security Check Point (SCP) 1, application of procedures for handling dangerous goods.

Detection of Malware in Android Phones Using Machine Learning

Abstract: In a major cyber security scare, around 1.5 crore Android devices in India have been infected by malware without the knowledge of the users. According to a report by cyber security solution firm Check Point Research in 2020, a new variant of mobile malware has quietly infected around 2.5 crore devices worldwide. Malware is any type of malicious software or code designed to harm a user's device, such as trojans, adware, ransomware, spyware, viruses or phishing apps. The permissions and API-calls are extracted from all Android applications, and both were included as features in the dataset. It is a process of analysing the malware binary without running the code. To offer a simple, streamlined, document-centric experience Jupyter Notebook interactive development environment and Flask is utilized. The Androguard tool and genetic algorithm analyses the APK files by separately extracting the permissions for each APK file. Supervised Machine Learning algorithms used are Support Vector Machine (SVM) and MLP an ANN numeral network approach is used to compare the traditional machine learning techniques. Experiments will be conducted on two types of models, traditional machine learning classifiers and deep learning neural networks. Initially, the classifiers are trained using the dataset, taken from android malware dataset and then testing and evaluationis performed based on the extracted features. An efficient method to detect the presence of malware in the android mobile phones using the permissions, API calls is implemented and the best classifier is identified which gives optimal results with accuracy, F-measure, Recall, and Precision scores. This would enable users to easily navigate various resources available with an adaptive user interface using android application.

Performance modeling of Licklider transmission protocol (LTP) via proactive transmission of signaling segments in deep‐space network

SummaryDelay‐tolerant networking (DTN) bundle protocol is considered one of the best transmission protocols to be used in space communications by NASA. There are studies that evaluated the performance, measuring the total transfer time of a complete file from sender to receiver, of the DTN protocol via simulation or emulated experiments beyond the real space‐based experiences. In addition, there is a very few additional research works available for the modeling of the Licklider transmission protocol (LTP). However, these past studies on LTP modeling are implemented as a Logarithmic approach that is based on the calculation of loss segments in file delivery. In this work, the approach is investigated in a different manner. Specifically, the performance model was created based on the probability of the segment's successful delivery on the LTP. Moreover, the original model is enhanced via introducing a burst of transfer and equal interval distribution of signaling segments, specifically check point (CP), along with the retransmission time out (RTO). The results from the developed model for the original DTN protocol and enhanced versions align with the results obtained by PC‐based testbeds.

CLOUD SECURITY: A REVIEW OF CURRENT ISSUES AND PROPOSED SOLUTIONS

Cloud technologies are currently one of the fastest growing directions in the IT field. This architecture uses virtualization technology in several computing paradigms (distributed systems, grid and service computing, etc.). It is possible to reach the goal using the unlimited possibilities of the Internet. It should be noted that most companies have transferred their resources and capabilities to cloud technology. According to Check Point Software Technologies Ltd 2020 statistics, 39% of enterprises said that security is important in cloud technology, and 52% said that public and hybrid cloud technologies have become more critical in the direction of security over the past two years. Enterprises are concerned about personal data storage and using special software enabled by cloud technologies. They are considering these points. This paper also discusses the various benefits of the cloud with its challenges and applications

Validity of Check Point Inhibitor (PD-1 and PD-L1) in Diagnosis of Gastric Adenocarcinoma Using Modified Tissue Elisa

Background: Checkpoint inhibitors (PD-1, PD-L1) are revolutionizing the oncology disease management process. Despite the fact that gastric cancer is a common malignancy with a poor prognosis, relatively little attention has been drawn and attracted to the treatment and diagnosis of this disease by using checkpoint inhibitor. James P. Allison and Tasuku Honjo were awarded the the Nobel Prize in Physiology and Medicine for their developments in fundamental science enabling checkpoint inhibitor therapies. Checkpoint inhibitor overexpression has been related to gastric cancer progression and clues for developing therapeutic goals as well as may provide diagnostic markers for gastric cancer. Aims: The aims of this study are firstly to detection of Checkpoint Inhibitors (PD-1, PD-L1) as novel diagnostics and prognostics markers first time in the world. Secondly, to investigate the validity of using (a modified tissue ELISA method) as a rapid, sensitive, low cost and specific diagnostic method in patients with gastric cancer. Patients and methods: Thirty gastric cancer patients were among patients who attending the Histopathology section -GIT hospital and Histopathology department- Teaching laboratories/ medical city teaching complex Baghdad / Ministry of Health, during the period from August 2020 to April 2021. Another 30 patients diagnosed with benign tumor, In addition, 30 apparently healthy people were chosen as a healthy control group. For these three groups, PD-1, PD-L1, using tissue ELISA technique was carried out. Results: The current study showed that the mean values of PD-1 in tissues of gastric cancer patients (133.413±53.126) was significantly higher (P=0.0001) in it in comparison to both benign tumor group (29.905±12.634) and control healthy group (21.775±12.489); for PD-L1 that the mean values of PD-L1 in tissues of gastric cancer patients (151.175±47.641) was significantly higher (P=0.0001) in it in comparison to both benign tumor group (72.565±9.945) and control healthy group (82.102±12.642); using receiver operating characteristic curve (ROC) area, which showed that area under the curve for PD-1 was (1.000) (p value 0.0001), while area under the curve for PDL-1 was (0.913) (p value 0.0001) and The cut off value for PD-1 associated with highest sensitivity and specificity (100%) was 40.2 ng/ml. The cut off value for PDL-1 associated with sensitivity (80%) and specificity (80%) was 51.6ng/ml. Conclusions: The present study showed that Checkpoint inhibitors (PD-1, PD-L1) values were significantly higher in patients affect with malignant gastric adenocarcinoma which may check a possible role of this marker in the progressing of the disease, furthermore the maximum sensitivity obtained from Checkpoint inhibitors (PD-1, PD-L1) was by using a cut off values equal to (40.2 ng/ml; 51.6 ng/ml) respectively. Therefore, Checkpoint inhibitors (PD-1, PD-L1) may be promising diagnostic tools especially at early stages and among patients at in promotion risk. Keywords: Checkpoint inhibitors (PD-1, PD-L1), gastric cancer.

Abstract 2080: LAG3-targeted IL15/IL15Rα-Fc (LAG3 x IL15) fusion proteins for preferential TIL expansion

Abstract The IL2Rβ/γc binding human cytokines IL2 and IL15 aid in the activation, proliferation, and survival of T and NK cells, and their therapeutic potential has been well established in animal models and human trials. However, therapeutic approaches utilizing these cytokines have suffered from low tolerability, fast clearance, and limited therapeutic window due to extensive activity on peripheral lymphocytes. Conversely, higher drug concentration and prolonged exposure are desirable to allow lymphocyte activation and proliferation at the tumor site, but this can be difficult to achieve due to dose-limiting toxicities associated with this axis. IL15 functions as a stabilized heterodimeric complex with membrane-bound IL15Rα on the surface of monocytes and DCs, which is presented in trans to lymphocytes expressing IL2Rβ/γc. We hypothesized that we could selectively target tumor-reactive TILs by combining a reduced potency IL15/IL15Rα heterocomplex with an immune checkpoint(CP)-targeting arm to bias binding and activation to CP-positive TILs, potentially improving therapeutic index. Lymphocyte activation gene 3 (LAG3) was chosen as the CP targeting-arm due to its frequent co-expression with PD1, bias to CD8+ T cells, ability to easily combine with anti-PD1 agents, and recent promising results with anti-LAG3 agents in the clinic. First, potency-reduced IL15/IL15Rα were created by engineering amino acid substitutions in IL15 - at the IL2Rβ/γc interface - that reduced in vitro potency by at least 1000-fold. We then designed LAG3 x IL15 fusion proteins containing single-chain IL15/IL15Rα and LAG3-targeting arms attached to a heterodimeric-Fc region, relying on targeting avidity to recover potency on LAG3+ cells. In vitro proliferation of lymphocytes in human PBMCs, stimulated with sub-optimal concentrations of anti-CD3 to induce LAG3 expression, was monitored by CFSE dilution or by counting Ki67+ cells after incubation with LAG3 x IL15 for 4 days. In vivo activity was evaluated using humanized mouse models by measuring the extent of human leukocyte expansion. Lead LAG3 x IL15 were evaluated for pharmacodynamic activity, pharmacokinetics, and tolerability in non-human primates. LAG3 x IL15 showed >500-fold selectivity compared to a non-targeted IL15 in an in vitro proliferation assay of lymphocytes stimulated for induced LAG3 expression. In vitro potency was greatest on effector memory CD8 T cells. LAG3 x IL15 were 3-fold more potent on CD8 T cells compared to CD4 T cells and had very weak activity on NK cells, consistent with minimal LAG3 expression on this population. In mouse models, treatment with LAG3 x IL15 promoted significantly increased numbers of T cells. Moreover, LAG3 x IL15 combined productively with anti-PD1 to promote additional T cell expansion. These results demonstrate that LAG3 x IL15 show a promising profile of selective IL15 delivery to TIL with minimal peripheral activity. Citation Format: Matthew J. Bernett, Suzanne Schubbert, Michael Hackett, Lukasz J. Ochyl, Lizett E. Scott, Christine Bonzon, Rumana Rashid, Kendra N. Avery, Irene W. Leung, Nicole Rodriguez, Connie Ardila, Umesh S. Muchhal, Norman J. Barlow, Rena Bahjat, John R. Desjarlais. LAG3-targeted IL15/IL15Rα-Fc (LAG3 x IL15) fusion proteins for preferential TIL expansion [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2080.

The Impact of The Immune Check Point Duration of use on Cost in Lung Cancer

Background: Monotherapy and combinations of Pembrolizumab (Pembro), Atezolizumab (Atezo) and Cemiplimab (Cemi), prolonged overall survival (OS) in advanced/metastatic non-small cell lung cancer (a/m NSCLC). Pembro demonstrated 5-year OS gain. The duration of therapy of the immune check point inhibitors (ICI) has not been defined. One-year adjuvant Durvalumab (Durv) and Atezo significantly prolonged OS. Neoadjuvant few cycles resulted in positive outcomes. Costs are relatively expensive, multiplying with prolonged use. The estimated 2019 CAR-T cost was $450,000. The Affordable Insulin bill 6833 capping insulin monthly cost at $35 was approved by the U.S. House of Representative. There are unmet needs for coherent drug cost policies and containment. We aimed 1- Explore the factors which impact ICI costs in lung cancer stages 2- Navigate cost-saving strategy based on generics, therapy duration and monotherapy utilization thresholds at $450,000 and $550,000 for combinations Methods: Clinical studies outcomes were quoted. Annual drug prices were calculated. Results: Estimated annual Pemetrexed (Peme) costs were $113,793, generic chemicals < $1,000 and Bevacizumab (Bev) $150,126 vs $148,000, mean 6 ICI. Pembro 2-year costs were $334,652. The 3- $501,978 and 5- $836,630 were above the $450,000. Atezo + Bev+ Peme combination had the highest 2-year $722,977 costs, above $550,000. Atezo + Peme costs were $422,725, Pembro + Peme $448,445 and Cemi + Peme $425,385, not significantly different. Costs decreased by 25% using generics. Extending ICI use by 6-12 months increased combination costs by 25-50%. Adjuvant 1-year Durv costs were $148,013 and Atezo $154,446, half the 2-year. Using response rates, cost of neoadjuvant Nivolumab (Nivo) 2-4 cycles were $25,000 - $50,000. Conclusion: Generics, short ICI duration use, neo-adjuvants, and utilization thresholds reduced costs.

Application of Value Stream Mapping to Improve Service in The Departure Terminal at Halim Perdanakusumah Airport

This study aims to identify and reduce waste in the passenger flow process at the Halim Perdanakusuma Airport departure terminal, so that passenger service remains good even with limited terminal capacity. This research used a qualitative method with a case study approach. The method stages are the observation of the departure passenger flow process mapped through current state Value Stream Mapping (VSM), distribution of questionnaires to obtain critical waste with Borda analysis, and fishbone diagrams to find out the rooting causes of critical waste, the proposing process improvements, and the future state of VSM, The results showed that critical waste in the flow of departure passengers is 22.11%, which includes passenger activities waiting for the Security Check Point 1 and Point 2 queue. Furthermore, based on the current state of VSM, the lead time for departure passengers is 33 minutes 47 seconds and VAR is 20.22%. While form the future state of VSM, the lead time is 28 minutes 22 seconds with a VAR of 20.36%, resulting in time efficiency of 5 minutes 24 seconds.

ANALISIS PENGAWASAN PETUGAS AVIATION SECURITY (AVSEC) DALAM MENDETEKSI BAHAN PELEDAK DI BANDAR UDARA KOMODO LABUAN BAJO

Aviation Security (AVSEC) officer still frequently discover dangerous goods in passenger luggage, such as scissors, knives, small gas cylinders, machetes/swords, razors, gas lighters, cutlery, a power bank that exceeds the limit, sea shells, pink sand, and marine life in the Prohibited Item category. Researchers also discovered that many passengers were bringing alcoholic beverages that were not labeled and exceeded the specified standards. This research aims 1) To discover how Aviation Security (AVSEC) officers play a part to aviation security and safety at Komodo Labuan Bajo Airport. 2) To determine what equipment is required to support Security Check Point (SCP) two in maintaining aviation security and safety at Komodo Labuan Bajo Airport. 3) To find out how Komodo Labuan Bajo Airport Aviation Security (AVSEC) officers handle dangerous explosive materials. This research uses qualitative methods. Data collection is carried out by observation methods, interviews, and documentation which are then carried out data analysis using data reduction, data presentation and conclusions. The results of this study reveal that 1) Aviation Security Officers (AVSEC) have a very important role in ensuring flight security and safety, 2) Passenger inspections on SCP 2 are carried out Security checks on SCP 2 must be supported by inspections with flight security aids, where inspections This is done by using X-Ray machine tools, Walk Through Metal Detector (WTMD), and Hand Hel Metal Detector (HHMD), 3) Aviation Security Officers (AVSEC) in handling explosives that are considered dangerous to all parties must carry out regular inspections. strict restrictions on passengers and goods that enter the area at Komodo Labuan Bajo Airport to prevent the transportation of prohibited and dangerous goods and can be used to threaten safety and security.