Respiratory syncytial virus. What's new in prevention?

This comprehensive review of Spirulina encompasses biotechnology, phycocyanin production, and purification. Bioactive compounds and vital nutrients were investigated during the study. The literature examines the potential therapeutic advantages and clinical applications of Spirulina. This analysis assesses Spirulina consumption and its associated health risks. The current review offers a comprehensive synthesis of the therapeutic applications as well as technologies utilized for the extraction and purification of phycocyanin. Moreover, this discourse delves into the examination of various advantageous techniques for extracting and purifying phycocyanin, encompassing physical, chemical, and enzymatic methods. The data derived from a multitude of studies strongly indicate the potential therapeutic applications of phycocyanin, encompassing its notable attributes as an antioxidant, anti-inflammatory agent, anticancer agent, antiviral agent, antimicrobial agent, antiallergic agent, anti-obesity agent, antihypertensive agent, and an immunological agent.

Tuberculous meningitis (TBM) is a critical form of tuberculosis with high morbidity and mortality. Paradoxical reactions (PR) are frequently observed in neurotuberculosis, with diverse manifestations. A selective immune dys/upregulation leads to cytokine surge. The exact immune pathogenesis is not known. This review explores the established literature-based knowledge in PR in HIV-ve TBM to visualize the gray zone in neurotuberculosis and possible immune therapeutic adventures. We undertook this systematic review as per the preferred reporting items for systematic reviews and meta-analyses guidelines and searched PubMed, Scopus, Embase, and Google Scholar database till July 25, 2024, to identify eligible studies focusing on PR in TBM/neurotuberculosis. Quality assessment followed the protocol of Murad MH et al. Data were synthesized narratively and statistically analyzed using Microsoft Excel. The search yielded 112 records describing 617 patients. PR is an immune dys/upregulated state in tuberculosis observed with a median age of 34 years (7-74 years), incidence of 12.7-64.7%, and 9.09-27.8% mortality. The spectrum involved clinical PR (tuberculomas, hydrocephalus, infarcts, arachnoiditis), imaging PR, cerebrospinal fluid PR, or in combinations. Treatment in the form of medical [corticosteroid, thalidomide, intrathecal hyaluronidase, biological (anti-tumor necrosis factor-alpha/TNF-α agents)], surgery (ventriculoperitoneal shunting) has shown good clinical response. Immunological and genetic studies in PR/neurotuberculosis are sparse. Immunological agents like corticosteroid, thalidomide, biologicals like anti-TNF-α have proven benefit in treating PR/neurotuberculosis. Research into the neuroimmunological and genetic aspects of PR is lacking and needs further exploration via predictive models and randomized therapy-based trials.

Trop2, Nectin-4, and PD-L1 expression profiles in esophageal squamous cell carcinoma: Implications for combined immunotherapy and ADC targeted therapies.

1612 Background: Financial toxicity in cancer care poses a significant burden for patients and healthcare systems. This study analyzed public data to evaluate the financial impact of oncology treatments, focusing on factors such as demographics, insurance type, gender disparities, or geographics. Methods: The 2022 Medical Expenditure Panel Survey (MEPS) data was analyzed, focusing on antineoplastic and immunologic agents. Cost distributions, payment sources, and financial burden—defined as prescription costs exceeding 20% of annual household income—were assessed across various insurances and demographic groups (age, gender, race, income, and education). Geographic analyses utilized Federal Information Processing Standard (FIPS) state codes. Results: The study included 1,379 oncology prescriptions. Prescription costs averaged 1,569 per prescription (median 388), ranging from 19 to 7,208. Annual costs spanned 2,507 (25th percentile) to 26,857 (75th percentile), with a median of 3,561 and a mean of 14,138. Non-prescription medical costs, such as procedures and hospitalizations, had a median of 45,475 and a mean of 47,509, with some exceeding 132,396 annually. Uninsured patients faced the highest average costs (78,439 annually), followed by Medicare patients (67,979). Medicaid patients had the lowest total costs (53,469). VA/TRICARE patients showed moderate costs (56,619) but higher prescription expenses (16,758). Low-income patients faced the greatest financial burden, spending 11.71% of their income on prescriptions, compared to 5.89% for middle-income and 2.66% for high-income patients. Private insurance beneficiaries faced the highest costs (5,500-6,000), particularly among Black and White patients, followed by Medicare (4,500-5,000). Medicaid beneficiaries incurred lower costs (3,500-4,000), while uninsured patients had the lowest mean costs (2,500-3,000), reflecting limited access to comprehensive treatments. Female patients had higher costs for breast and lung cancer treatments. Black and Hispanic patients relied more on Medicaid. Patients with graduate degrees had higher average costs (4,226) than those with a high school education or less (3,707). Geographically, financial burden was highest in the Midwest, moderate in the Northeast, and mixed in coastal and Southern states. Conclusions: Significant disparities in financial toxicity exist across demographics, insurance types, and regions. The gap between mean and median costs underscores the disproportionate financial strain faced by some patients. Policy interventions, including expanded insurance coverage, capped out-of-pocket costs, and targeted subsidies, are needed to improve equity and affordability in cancer care.

Numerous medications have been associated with an increased risk of vaginal hemorrhage in women. In this study, we analyzed data from the FDA Adverse Event Reporting System (FAERS), focusing on reports of drug-induced vaginal bleeding in women. Risk signals were assessed using disproportionality analyses, specifically the reporting odds ratio (ROR) and the proportional reporting ratio (PRR), to identify significant associations between drugs and adverse events. We found that anticoagulants, hormonal drugs, psychotropic drugs, hypoglycemic agents, antineoplastic agents, anti-inflammatory drugs, immunological agents, and some drugs for osteoporosis were significantly associated with the risk of vaginal hemorrhage. Hormonal drugs, anticoagulants, and particularly antifungal agents were attributed to a notably high proportion of vaginal hemorrhage cases, necessitating further investigation into the underlying mechanisms. Therefore, precise clinical management of medications and optimization of treatment regimens are necessary to reduce the risk of vaginal hemorrhage and improve safety.

Considering the limited treatment options for acute lung injury (ALI) and pulmonary fibrosis (PF), ozone treatment may be promising as a new immunological agent with its ability to modulate cytokines and interferons. We aimed to investigate the effects of inhaled ozone therapy on both ALI and PF in rat models. A total of 48 albino Wistar male rats were included in the study. Lipopolysaccharide (LPS) was used to induce the ALI model, and bleomycin was used for the PF model. The effects of inhaled ozone (O3) were investigated using the ELISA method. Hematoxylin&eosin staining, Masson's trichrome staining, and immunohistochemical methods were used for histopathological evaluation. The Interleukin-1 beta (IL-1β), Interleukin-6 (IL-6), Tumor Necrosis Factor-alpha (TNF-α), and Nuclear Factor kappa B subunit p65 (NF-κB p65) levels in the ALI + 0.08 ppm O3, ALI + 0.12 ppm O3, PF + 0.08 ppm O3, and PF + 0.12 ppm O3 groups statistically decreased to the same extent and approached the levels of control animals. It was observed that IL-1β, IL-6, TNF-α, and NF-κB p65 levels in lung tissues were significantly and dose-dependently decreased compared to the untreated PF and ALI groups, respectively. While fibrosis was severe in the PF + 0.08 ppm O3 group, it decreased to more moderate levels in the PF + 0.12 ppm O3 group. The cytokine levels confirmed that inhaled ozone protected the lungs from both ALI and the development of PF.

For resectable adenocarcinoma of the esophagogastric junction (AEG), current treatment exploration primarily focuses on perioperative chemotherapy regimens combined with PD-1/PD-L1 inhibitors, but the long-term survival benefits of still require further investigation, and the use of upfront immunotherapy is typically restricted to patients with metastatic MSI-H (M1 MSI-H) disease due to their potential responsiveness to immunological agents. Adebrelimab, as a novel PD-L1 antibody, has not yet been proven for its efficacy and safety in adenocarcinoma of the esophagogastric junction. The AEGIS study is a prospective, open-labeled, single-arm, phase II clinical trial. A total of 26 patients with AEG will be enrolled. The primary endpoint is the pathologic complete response (pCR) rate after perioperative neoadjuvant immunochemotherapy. Secondary outcomes of the study include the objective response rate (ORR), R0 resection rate, major pathological response (MPR) rate, and pCR rate in combined positive score(CPS) ≥ 5 and MSI-H populations, event-free survival (EFS), and overall survival (OS). The exploratory outcomes are the biomarkers related to therapeutic efficacy, such as PD-L1 expression, microsatellite instability (MSI), tumor mutational burden(TMB), Epstein-Barr virus(EBV) infection, and circulating tumor DNA(ctDNA). This trail aims to verify the efficacy and safety of the perioperative treatment regimen of anti-PD-L1 (Adebrelimab) combined with chemotherapy (capecitabine plus oxaliplatin, XELOX) for patients with resectable AEG. Considering the differences in chemotherapy regimen tolerance between Asian and Western populations, this study intends to evaluate the suitability of Adebrelimab combined with XELOX chemotherapy for the Asian population. ClinicalTrials.gov: NCT06482788. The trial was prospectively registered on 22 May 2024, https://clinicaltrials.gov/study/NCT06482788 .

Leeches are widely used as model organisms in scientific studies and medical treatments. Medical leeches are hematophagous parasites that usually feed on the blood of their hosts. Some leeches show deformities, usually after feeding. This causes both medical and economic losses as it reduces the effectiveness of leeches in cultivation and medical treatment. The aim of this study was to investigate the effects of morphological deformations after feeding in Hirudo verbana, Carena 1820 (Annelida, Hirudinea), an important species in medical leech treatments. For this purpose, both histopathological and scanning electron microscopy examinations of starved and fed leeches were performed. The causes of deformities in medical leeches were found to be due to overfeeding, which caused cracks on the intestinal surface and therefore deterioration of the tissues. It is also thought that the immunological agents in the fed blood destroyed the medical leech tissue in these regions. In addition, it was determined that the cellular structure of the shaped blood elements stored in the cavity after feeding was preserved for a long time (months) without deterioration. It is certain that revealing the mechanism by which this occurs will inspire the preservation of blood for a long time in blood transfusion.

To facilitate the translation of immunotherapies from bench to bedside, predictive preclinical models are essential. We developed the in vivo immuno-oncology Hollow Fiber Assay (HFA) to bridge the gap between simpler cell-based in vitro assays and more complex mouse models for immuno-oncology drug evaluation. The assay involves co-culturing human cancer cell lines or primary patient-derived cancer cells with human immune cells inside semipermeable hollow fibers. Implanted intraperitoneally in mice, the fibers captured treatment-induced immune cell-mediated cancer cell killing following treatments with aCD3 and/or IL-2, demonstrating the feasibility of the assay. Traditional models require lengthy observation periods to monitor tumor growth and treatment response. The immuno-oncology HFA enables a rapid initial in vivo evaluation of immunological agents on cancer and immune cells of human origin, addressing two of the 3Rs — reduction and refinement — in animal research.

Improved MRD Clearance By Incorporating Venetoclax into Pediatric-Inspired Regimen in Newly Diagnosed Adolescent and Adult Patients with Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia

An extend-policy iterative algorithm is proposed for solving the ecological evolving-lung cancer cells growth inhibition optimal drug delivery scheme. With the analysis of the cell proliferation-apoptosis process of lung cancer cells with primitive immune system and external drug interventions, such as chemotherapeutic drugs and immunological agents, a model of ecological containment of lung cancer cells mimicking injection labeling is constructed. The HJB equation for biological tissue damage has also been established by considering the concentration of lung cancer cells in the blood and the amount of drug administered. The final simulation experiment proved the effectiveness of the drug delivery scheme.

Background/Objectives: Cancer remains one of the leading causes of death, with breast, liver, and pancreatic cancers significantly contributing to this burden. Traditional treatments face issues including dose-limiting toxicity, drug resistance, and limited efficacy. Combining therapeutic agents can enhance effectiveness and reduce toxicity, but separate administration often leads to inefficiencies due to differing pharmacokinetics and biodistribution. Co-formulating hydrophobic chemotherapeutics such as paclitaxel (PTX) and hydrophilic immunologic agents such as polyinosinic-polycytidylic acid (Poly IC) is particularly challenging due to their distinct physicochemical properties. This study presents a novel and efficient approach for the co-delivery of PTX and Poly IC using chitosan-based nanoparticles. Method: Chitosan-PEG (CP) nanoparticles were developed to encapsulate both PTX and Poly IC, overcoming their differing physicochemical properties and enhancing therapeutic efficacy. Results: With an average size of ~100 nm, these nanoparticles facilitate efficient cellular uptake and stability. In vitro results showed that CP-PTX-Poly IC nanoparticles significantly reduced cancer cell viability in breast (4T1), liver (HepG2), and pancreatic (Pan02) cancer types, while also enhancing dendritic cell (DC) maturation. Conclusions: This dual-modal delivery system effectively combines chemotherapy and immunotherapy, offering a promising solution for more effective cancer treatment and improved outcomes.

The Centers for Medicare and Medicaid Services (CMS) recently announced the Maximum Fair Price for the first 10 Medicare Part D drugs selected for price negotiation. By February 2025, CMS should announce the list of Part D drugs to be negotiated with implementation of the negotiated prices in 2027. To identify up to 15 Medicare Part D single-source drugs anticipated to be selected by CMS for price negotiation in 2025. We followed selection criteria identified in the Inflation Reduction Act and CMS guidance to identify drugs. We projected 2023 Part D gross spending using 2020-2022 data reported by CMS and linear prediction models. We ranked products according to the projected spending figure and identified those not eligible for selection because of (1) number of years since approval, (2) availability of a biosimilar or generic version, (3) approval for a single orphan indication, (4) whole human blood or plasma-derived, or (5) eligibility for the small biotech exception. We identified 13 products likely subject to Medicare drug price negotiation, including 4 anticancer therapies, 3 noninsulin antidiabetic products, 2 inhalers, 1 antifibrotic therapy, 1 gastrointestinal agent, 1 enzyme replacement therapy, and 1 product indicated for dyskinesia. These 13 products each had projected annual gross Part D spending more than $1 billion. We identified 7 additional products with uncertainty to complete the list of 15, including an insulin, an antiviral, an antibiotic, an immunologic agent, an antidiabetic, and 2 cancer drugs. These products had projected gross Part D spending between $877 million and $1.399 billion. Twenty-two products with comparable levels of spending were deemed ineligible for selection because of availability of a generic or biosimilar version (10 products), insufficient years since approval (8 products), eligibility for the small biotech exception (3 products), and expected market discontinuation (1 product). Our identification of products anticipated to be selected for negotiation in 2025 (with implementation of negotiated prices in 2027) will help inform manufacturers, payers, patients, and policymakers of the products that will likely see a decrease in Medicare drug prices as result of negotiation. We identified 22 products with levels of spending that are comparable with those anticipated to be selected for negotiation but are not eligible, primarily because of generic or biosimilar availability or insufficient time on market.

Abstract Background: Standard therapies provide marginal benefits in overall survival and leading immunologic agents have proven ineffective in the immunologically cold environment of pancreatic ductal adenocarcinoma (PDAC). Current standard of care chemotherapies experience demonstrable resistance in the clinical setting with primary and secondary resistance frequently leading to poor outcomes. Oncolytic virus (OV) therapies are emerging as an avenue of therapeutic potential with vesicular stomatitis virus (VSV) providing an onco- selective platform with potential for rapid replication and minimal outside virulence. The aim of this project is to determine if the addition of OV to the standard systemic treatments would result in a synergistic improvement of the therapeutic efficacy, and investigate the potential mechanisms involved. Methods: A VSV variant containing the Morreton G protein inserted into a wild-type VSV backbone (VMG)was propagated and purified for in vitro and in vivo studies. In vitro studies investigating oncolytic potential and viral kinetics of VSV in combination with FOLFIRINOX (FFX) and Gemcitabine Paclitaxel (GP) therapies were compared to monotherapy in multiple cell culture formats including 2D Monolayer, 3D Spheroid, and ongoing investigation into patient derived organoids. Proteomics analysis of monotherapies along with combination therapy was performed on in vitro cultures. Ongoing in vivo studies are investigating the therapeutic potential of concurrent treatments. Results: Cytotoxicity assay studies of equivalent multiplicities of infection (MOI) demonstrated increased cytotoxicity of combination therapy (Percent viable 10.2% ± 1.3%) compared to virus alone (30.7% ± 1.9%) or FFX alone (84.4% ± 6.6%) in Hs766T PDAC cell lineAsPC-1 cell line demonstrated similar effects with minimal cytotoxicity from FFX alone (100% ± 5%) with comparable resistance to virus alone (69.9% ± 1.8%) in comparison to combination therapy (40.3% ± 1.0%). Additional cell lines including Panc-01 and MiaPaCa2 provided similar results. Treatment of formed spheroids with combination therapy resulted in reduction in overall size of spheroid along with increased Viral GFP marker fluorescence, in combination group, compared to monotherapy with each treatment. Proteomic analysis investigating concomitant treatment with both standards of care produced unique expression profiles. Multiple pathways including cell cycle regulation, apoptosis, MAPK signaling, PI3K-Akt signaling, ErbB signaling showed significant regulatory changes in protein expression across all treatment groups. Conclusion: VSV oncolytic virus in conjunction with standard of care therapy demonstrates a potentially effective approach for synergistic enhancement of the therapeutic efficacy against PDAC. Ongoing research is investigating the immunomodulatory and metabolic effects of both monotherapies in conjunction with combination therapy to further determine the synergistic mechanisms involved and how they can be further utilized to overcome treatment resistance in PDAC. Citation Format: Conner Hartupee, Amirsalar Mansouri, Joycelynn Coleman-Barnett, Dana Adamcova, Dorota Wyczechowska, Bolni Marius Nagalo, Mulu Tesfay, Jovanny Zabaleta, Luis Del Valle, John West, Jiri Adamec, Omeed Moaven. Oncolytic virotherapy as an effective tool to synergistically enhance therapeutic efficacy of standard systemic treatments for pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr B049.

Abstract Background Neoadjuvant chemoradiotherapy (nCRT) has been established as a standard treatment for locally advanced esophageal squamous cell carcinoma (SqCC), but there are still insufficient research advances on the incorporation of immunologic agents. The aim of this study was to explore immune microenvironment changes before and after nCRT. Methods A total of 101 patients who underwent nCRT followed by radical surgery for esophageal SqCC in a single institution between 2005 and 2021 were analyzed. Pre-nCRT endoscopic biopsy and post-nCRT surgical specimen were evaluated using tissue microarray. Immunohistochemical staining for CD3, CD8, and PD-L1 were performed. Tumor-infiltrating lymphocytes (TIL) density were independently evaluated by blinded pathologist (total number of 2+ to 3+ cells/total area (mm2)). Results Compared to pre-nCRT biopsy, PD-L1 expression (8.7% vs. 14.0%, p<0.001) and TIL density (259.1 vs. 566.9, p<0.001) were significantly increased in surgical specimen after nCRT. When divided into groups according to nCRT response, post-nCRT TIL density (p=0.341), fold changes of TIL density (p=0.749), and PD-L1 expression (p=0.642) were not significantly different between ypCR (n=23) and non-ypCR group (n=78). In ypT0 group (n=36), post-nCRT TIL density was marginally higher than that of non-ypT0 group (404 vs. 259, p = 0.050). Conclusion Irrespective of clinical responses, PD-L1 expression and TIL density were both increased after nCRT. Our results could help the development of combination strategy of immunologic drugs and seek the possibility of an organ-saving strategy that will contribute to improving quality of life of patients.

ABSTRACT Background The objective of this study was to evaluate the reporting associations between Central serous chorioretinopathy (CSCR) and many available drugs using FAERS. Research design and methods FAERS reports from 2004 to 2023 were included in the study. The Medical Dictionary for Regulatory Activities (MedDRA) was used to identify CSCR cases. Reporting odds ratios (RORs) and corresponding 95% confidence intervals (CIs) for the reporting associations between available drugs and CSCR were calculated. A reporting association was considered statistically significant when the lower limit of the 95% CI was > 1.0. Results There were 1002 reports of 110 drugs with suspected drug-associated CSCR based on the ‘primary suspects’ role code in the FAERS database found to have statistically significant signals. Among the top 20 ROR drugs, the most frequently reported drugs were dermatological drugs (ATC:D, 210 cases, 64.41%), followed by antitumor agents and immunological agents (ATC:L,77 cases, 23.62%), Systemic Hormonal Preparations, Excl. Sex hormones and Insulins (ATC:H, 19 cases, 5.80%) and sensory organ drugs (ATC:S, 9 cases, 2.76%). The top 3 drugs associated with CSCR were Prednisolone (144 cases, 44.17%), Fluticasone (29 cases, 8.90%), and Methylprednisolone (27 cases, 8.28%). Conclusions This is the first real-world study using FAERS database to investigate drug-induced CSCR. Clinicians and pharmacist must keep in mind CSCR is a serious ocular complication associated with glucocorticoids, tyrosine kinase receptor inhibitor, and other drugs that can cause CSCR.

Optimization of spermatozoa analysis in mice: A comprehensive protocol

In the precision medicine era, identifying predictive factors to select patients most likely to benefit from treatment with immunological agents is a crucial and open challenge in oncology. This paper presents a pan-cancer analysis of Tumor Mutational Burden (TMB). We developed a novel computational pipeline, TMBcalc, to calculate the TMB. Our methodology can identify small and reliable gene signatures to estimate TMB from custom targeted-sequencing panels. For this purpose, our pipeline has been trained on top of 17 cancer types data obtained from TCGA. Our results show that TMB, computed through the identified signature, strongly correlates with TMB obtained from whole-exome sequencing (WES). We have rigorously analyzed the effectiveness of our methodology on top of several independent datasets. In particular we conducted a comprehensive testing on: (i) 126 samples sourced from the TCGA database; few independent whole-exome sequencing (WES) datasets linked to colon, breast, and liver cancers, all acquired from the EGA and the ICGC Data Portal. This rigorous evaluation clearly highlights the robustness and practicality of our approach, positioning it as a promising avenue for driving substantial progress within the realm of clinical practice.

Abstract Background: Immune recognition and cytotoxic responses play an important role in the pathogenesis and progression of cutaneous squamous cell carcinoma (cSCC). Talimogene laherparepvec (TVEC) is an HSV-1 oncolytic immunological agent FDA approved for the local treatment of unresectable recurrent melanoma. It is proposed that T-VEC directly destroys cancer cells, and induces production of GM-CSF to enhance systemic antitumor immune priming. This proposed mechanism of action supports the novel approach to implement TVEC in the management of cSCC, particularly, in patients with increased burden of primary tumors. Methods: Study subjects were Immunocompetent, ≥ 18 years of age, and diagnosed with at least one histologically confirmed primary low-risk cSCC according to the Brigham and Women staging system. Unresectable lesions or patients unable/unwilling to undergo standard of care treatment were eligible to participate. Study lesions included target lesions injected (TLIs) and target non-injected lesions (TNILs). TNILs were selected to evaluate for abscopal effect when feasible. The TLIs were treated according to TVEC FDA approved protocol and followed for 1yr after the 1st injection. The primary study endpoint was to evaluate the overall response rate, defined as the proportion of subjects who achieved complete response and partial response in the TLIs. Safety and adverse effect profile (AEs), duration of response, time to response, durable response rate, and time to progression, were the secondary endpoints. A Simon 2 stage design was used. Total sample size was calculated to be 20 subjects. A total of 11 subjects were recruited, due to the COVID-19 pandemic and 100% CR observed in the interim analysis. NCT 03714828. Results: The analysis was conducted after all 11 participants completed Visit 8 (230-271 days from study initiation). Conclusions: TVEC showed extremely impressive ORR for patients with cSCC with a 95.8% CR for TLIs. AE profile of TVEC was mild and was well tolerated. Further studies evaluating the role of intralesional immunotherapy should be considered in patients with increased burden of cSCC. Table 1. summarizes the study results. For the primary endpoint 100% of participants achieved an overall response. Primary outcomes for patients (n = 11) Secondary outcomes for TLIs (n = 24) Time to response - days Mean ± standard deviation Median/Range (min, max) 41.6 ± 24.9 Time to response - days Mean ± standard deviation Median/Range (min, max) 48.7 ± 29.2 35/(18 - 112) 35/(18 - 112) Final response to TVEC - % Overall response rate (ORR) Partial response (PR) Complete response (CR) 100% (11/11) 9.1% (1/11) Response to TVEC - Overall response rate (ORR) Partial response (PR) Complete response (CR) 100% (24/24) 90.9% (10/11) 4.2% (1/24) 95.8% (23/24) Duration of response - days Mean ± standard deviation Median - Range (min, max) 206.0 ± 26.0 Duration of response - days Mean ± standard deviation Median - Range (min, max) 201.4 ± 29.6 212 (140 - 236) 209 (136 - 250) Durable response rate - % 90.9% (10/11) Durable response rate - % 83.3% (20/24) Secondary outcomes for TNILs (n = 2) Final response to TVEC - % 100% (2/2) Adverse Events NCI CTCAE (v. 4.0) Event n (%) 95% CI Severity Mild (Grade 1) Moderate (Grade 2) Fatigue 5 (45.5%) (16.7%, 76.6%) 4 (80%) 1 (20%) Flu-like symptoms 4 (36.4%) (10.9%, 69.2%) 3 (75%) 1 (25%) Headache 2 (18.2%) (2.3%, 51.7% 2 (100%) Citation Format: Clara Curiel-Lewandrowski, Delaney B. Stratton, Anngela C. Adams, Haiyan Cui, Denise Roe, Srinath Sundararajan. A single arm phase 2 study of TVEC in patients with invasive cutaneous SCC: A novel therapeutic approach for low risk tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT004.