tbuckley/cabot-search huggingface dataset:
FRONTiER: A feasibility trial of nivolumab with neoadjuvant CF or DCF, FLOT therapy for locally advanced esophageal carcinoma (JCOG1804E)—Short-term results for cohorts C and D.
Authors: Satoru Matsuda, Shun Yamamoto, Ken Kato, Hiroyuki Daiko, Takashi Kojima, Hiroki Hara, Tetsuya Abe, Yasuhiro Tsubosa, Hirofumi Kawakubo, Kengo Nagashima, Kazunori Aoki, Shinichi Yachida, Yuko Kitagawa
Journal: Journal of Clinical Oncology (2022)

286 Background: The standard neoadjuvant chemotherapy (NAC) in Japan for locally advanced esophageal squamous cell carcinoma (ESCC) consists of CDDP + 5-FU (CF). Recently, neoadjuvant DTX plus CF (DCF) therapy has shown promising efficacy for locally advanced ESCC. In addition, immune checkpoint inhibitors (ICIs) have demonstrated a survival benefit in ESCC and potential as an NAC in several cancers, including lung, breast, skin, and bladder. We previously reported that neoadjuvant CF plus nivolumab (Nivo) therapy was tolerable and showed promising efficacy for ESCC; however, the efficacy of ICI with DCF as an NAC and the safety of subsequent surgery for ESCC patients remain unclear. Methods: FRONTiER is a multi-cohort phase I study designed to evaluate the safety and efficacy of ICI combined with NAC in ESCC. The eligibility criteria were histologically proven ESCC with cT1N1-3M0 or cT2-3N0-3M0 (8th-UICC TNM classification), patient age of 20-75 years, PS ≤1, and no prior cancer therapies. The primary endpoint was the incidence of dose-limiting toxicities (DLT) from the initial dose to the 30th postoperative day. This study contained 5 experimental cohorts: cohort C received 3 courses of DTX (70 mg/m 2 ), CDDP (70 mg/m 2 ), and Nivo (360 mg/body) on day 1 and 5-FU (750 mg/m 2 ) on days 1–5 every three weeks. Cohort D received one administration of Nivo (240 mg/body) 2 weeks before chemotherapy followed by the same regimen as cohort C. Results: Twelve patients were enrolled in cohort C (n = 6) and D (n = 6) (median age [range]: 60 [31-74] years, PS 0/1: 11/1, clinical stage I/II/III/IVA: 2/2/7/1). Only one patient in cohort D developed DLT (grade 3 dyspnea and rash); no other DLT were seen. Grade ≥3 adverse events were neutropenia (n = 1), leukopenia (n = 7), anorexia (n = 3), hyponatremia (n = 2), febrile neutropenia (n = 1), nausea (n = 1), and lymphopenia (n = 1) during NAC, and lung infection (n = 2), peritoneal infection (n = 1), anemia (n = 1), lymph leakage (n = 1), vagal reflex (n = 1), dyspnea (n = 1), rash (n = 1), septic shock (n = 1), pleural effusion (n = 1), and pneumatosis intestinalis (n = 1) during the postoperative period. No treatment-related deaths were observed. All patients received 3 courses of NAC, and 11 patients (91.7%) achieved an R0 resection without treatment interruption. One patient (16.7%) in cohort C and 3 patients (50.0%) in cohort D achieved pathological complete responses. Conclusions: Neoadjuvant DCF + Nivo with/without prior Nivo administration followed by surgery for locally advanced ESCC was well tolerated and showed an extremely promising efficacy. Clinical trial information: NCT03914443.
The International Leprosy Conference at Berlin
Journal: BMJ (1897)

amalgamate the two institutions and thus encourage the growth of thrifty habits ?" Dr. FBANCIS WARING then moved :-"That this meeting is of opinion that the time has arrived when an investigation should be held into the mode of administering medical relief in the hospitals and dispensaries of Brighton and Hove, and it is further of opinion that this investigation should be conducted by a committee which should be rep esentative of all interests con- cerned."In moving the resolution he disclaimed all unfriendly spirit to the institutions of the town, but he believed that some step should be taken to safeguard their charities against abuse.
Correction: Early nasal type I IFN immunity against SARS-CoV-2 is compromised in patients with autoantibodies against type I IFNs
Authors: Jonathan Lopez, Marine Mommert, William Mouton, Andrés Pizzorno, Karen Brengel-Pesce, Mehdi Mezidi, Marine Villard, Bruno Lina, Jean-Christophe Richard, Jean-Baptiste Fassier, Valérie Cheynet, Blandine Padey, Victoria Duliere, Thomas Julien, Stéphane Paul, Paul Bastard, Alexandre Belot, Antonin Bal, Jean-Laurent Casanova, Manuel Rosa-Calatrava, Florence Morfin, Thierry Walzer, Sophie Trouillet-Assant
Journal: The Journal of Experimental Medicine (2021)

The authors regret that in the original version of this paper, Hadjadj et al. ( 2020) was cited instead of Bastard et al. (2020) in a sentence about auto-Abs in the Introduction.The corrected sentence is below."This defect is explained in some patients by inborn genetic defects of IFN-I induction or amplification (Zhang et al., 2020b) and in others by the presence of neutralizing autoantibodies (auto-Abs) against type I IFNs, mainly IFN-α and/or IFN-ω and, in rare cases, IFN-β (Bastard et al., 2020).
How covid-19 vaccines exposed India’s adverse events reporting system
Authors: Priyanka Pulla
Journal: BMJ (2022)

Adverse events are among the most heavily scrutinised parts of the covid-19 vaccine process. But India's system was woefully unprepared for this, leaving families confused, sowing vaccine hesitancy in communities, while robbing the system of valuable data, reports <b>Priyanka Pulla</b>
Book Review
Authors: Giovanni A. Fava, David O. Antonuccio, William G. Danton, Garland Y. DeNelsky, RogerP. Greenberg, James S. Gordon, Luigi Grassi, Roberto Righi, Shariar Makoui, Laura Sighinolfi, Stefano Ferri, Florio Ghinelli, Kazutoshi Nakamura, Yoshihiko Hoshino, Atsushi Watanabe, Kyoichi Honda, Shinichi Niwa, Masaharu Yamamoto, Brunna Tuschen-Caffier, Irmela Florin, Walter Krause, Martin Pook, Toru Uehara, Kaoru Sakado, Miwako Sakado, Tetsuya Sato, Toshiyuki Someya, Ursula Pauli-Pott, Alexander Darui, Dieter Beckmann, Geert A.C. Vervaeke, Theo K. Bouman, Lucia R. Valmaggia, Paolo Santonastaso, Tatiana Zanetti, Silvia Ferrara, Maria C. Olivotto, Nicola Magnavita, Angela Favaro
Journal: Psychotherapy and Psychosomatics (1999)
Flexibly Deformable Collagen Hydrogel Tube Reproducing Immunological Tissue Deformation of Blood Vessels as a Pharmacokinetic Testing Model (Adv. Healthcare Mater. 1/2022)
Authors: Shun Itai, Hiroaki Onoe
Journal: Advanced Healthcare Materials (2022)

Collagen Hydrogels In article number 2101509 by Shun Itai and Hiroaki Onoe, an immunological deformation reaction of blood vessels is reproduced on a flexibly deformable collagen tube device both at the tissue and cell levels. An inflammatory mediator induces contraction of endothelial cells and shrinkage of the vessel tissue thanks to the self-standing collagen tube. The traction force is calculated by numerical analysis, and drug screening was demonstrated with an anti-histamine material.
Antibody Response Six Months after SARS-CoV-2 mRNA Vaccination in Patients with Inflammatory Bowel Disease
Authors: Sarah Frey, Reezwana Chowdhury, Caoilfhionn M Connolly, William A Werbel, Dorry L Segev, Alyssa M Parian
Journal: Clinical Gastroenterology and Hepatology (2022)
Sodium, potassium, and rate of constants for sodium efflux in leucocytes from hypertensive Jamaicans.
Journal: BMJ (1981)

Leucocyte sodium and potassium content and concen- trations were measured along with ouabain-sensitive and ouabain-insensitive rate constants for sodium efflux in 14 controls and 20 black patients with essential hypertension.Leucocyte sodium content was significantly increased in the patients (mean 101-1±7-8 mmol/kg dry solids v 745 + 76 mmol/kg dry solids; p <0 05), whereas the rate constants for sodium efflux were not significantly reduced.There was no difference between the two groups in cell potassium values.The increase in leucocyte sodium content in the presence of normal rate constants for sodium efflux suggests an increase in membrane permeability to sodium, which might be important in the pathogenesis of essential hypertension.
Asthma in the elderly: Diagnosis and management
Journal: Journal of Allergy and Clinical Immunology (2010)

Learning Objectives: ''Asthma in the elderly: Diagnosis and management'' 1.To understand the uniqueness of the immune system in the geriatric patient.2. To be able to direct therapies to best serve the uniqueness of the geriatric patient.3. To improve outcomes in geriatric patients with immune-mediated disease.
Long-Term Results of the RAPCO Trials
Authors: Brian F. Buxton, Philip A. Hayward, Jai Raman, Simon C. Moten, Alexander Rosalion, Ian Gordon, Siven Seevanayagam, George Matalanis, Umberto Benedetto, Mario Gaudino, David L. Hare, Jullien Gaer, Justin Negri, Masashi Komeda, Rinaldo Bellomo, Laurie Doolan, Larry McNicol, John Brennan, Robert Chan, David Clark, Ronald Dick, Anthony Dortimer, David Ecclestone, Omar Farouque, Dharsh Fernando, Mark Horrigan, Anthony Jackson, Leslie Oliver, Nilesh Mehta, Voltaire Nadurata, Nim Nadarajah, George Proimos, Michael Rowe, Ben Sia, Christopher Webb, Nagesh Anaveker, Peter Barlis, Paul Calafiore, Boniface Chan, John Cotroneo, Jennifer Johns, Elizabeth Jones, Paul Kertes, David O’Donnell, Stephen Sylviris, Anew Tonkin, Robert Fabini, Leighton Kearney, Ruth Lim, Maurice Molan, Gerard Smith, Chris Wellman, John Eng, Irbaz Hameed, Margaret Shaw, Sana Gerbo
Journal: Circulation (2020)

Background: An internal thoracic artery graft to the left anterior descending artery is standard in coronary bypass surgery, but controversy exists on the best second conduit. The RAPCO trials (Radial Artery Patency and Clinical Outcomes) were designed to compare the long-term patency of the radial artery (RA) with that of the right internal thoracic artery (RITA) and the saphenous vein (SV). Methods: In RAPCO-RITA (the RITA versus RA arm of the RAPCO trial), 394 patients &lt;70 years of age (or &lt;60 years of age if they had diabetes mellitus) were randomized to receive RA or free RITA graft on the second most important coronary target. In RAPCO-SV (the SV versus RA arm of the RAPCO trial), 225 patients ≥70 years of age (or ≥60 years of age if they had diabetes mellitus) were randomized to receive RA or SV graft. The primary outcome was 10-year graft failure. Long-term mortality was a nonpowered coprimary end point. The main analysis was by intention to treat. Results: In the RA versus RITA comparison, the estimated 10-year patency was 89% for RA versus 80% for free RITA (hazard ratio for graft failure, 0.45 [95% CI, 0.23–0.88]). Ten-year patient survival estimate was 90.9% in the RA arm versus 83.7% in the RITA arm (hazard ratio for mortality, 0.53 [95% CI, 0.30–0.95]). In the RA versus SV comparison, the estimated 10-year patency was 85% for the RA versus 71% for the SV (hazard ratio for graft failure, 0.40 [95% CI, 0.15–1.00]), and 10-year patient survival estimate was 72.6% for the RA group versus 65.2% for the SV group (hazard ratio for mortality, 0.76 [95% CI, 0.47–1.22]). Conclusions: The 10-year patency rate of the RA is significantly higher than that of the free RITA and better than that of the SV. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT00475488.
What's new in the other general journals
Authors: Alison Tonks
Journal: BMJ (2006)

Sixty years after atomic bombs dropped on Hiroshima and Nagasaki, researchers are still studying the effects of radiation exposure on the local population. In the latest cross sectional study of survivors, over half the women (1397/2739, 51%) and nearly a third of the men (436/1352, 32%) had thyroid disease, and 15% of the whole cohort had solid nodules, 2% had cancers (mostly papillary), and 8% had benign cysts. Credit: JAMA Using sophisticated techniques to measure radiation exposure and equallysophisticated techniques to look for thyroid disease, the researchers found a clear link between radiation dose and the prevalence of all thyroid nodules. They estimated that 37% of cancers, 31% of benign nodules, and 25% of thyroid cysts in this elderly cohort were caused directly by radiation from the two bombs. Survivors aged under 10 at the time seemed most vulnerable, presumably because their thyroid glands were more radiosensitive than those of young adults. The researchers found no dose-response relation between radiation dose and autoimmune thyroid disease, however, which tips the weight of evidence against a causal link between the two. JAMA 2005;295: 1011–22 [OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4] European scientists have developed a new vaccine that seems to protect young children against otitis media. The vaccine contains antigenic material from 11 different serotypes of Streptococcus pneumoniae , each one carried by a protein derived from Haemophilus influenzae . Between them, these pathogens are the most important causal agents of otitis media in young children. In a randomised trial, the new vaccine reduced by about a third the overall incidence of otitis media among children under 2 years in the Czech Republic and Slovakia (333/2455, 14% v 499/2452, 20%). The 2455 vaccinated children were 57.6% (95% CI 41.4 to 69.3) less likely to develop otitis media caused by S pneumoniae and 35.3% (1.8% to 57.4%) less likely to develop otitis … [1]: {openurl}?query=rft.jtitle%253DJAMA%26rft.stitle%253DJAMA%26rft.issn%253D0002-9955%26rft.aulast%253DImaizumi%26rft.auinit1%253DM.%26rft.volume%253D295%26rft.issue%253D9%26rft.spage%253D1011%26rft.epage%253D1022%26rft.atitle%253DRadiation%2BDose-Response%2BRelationships%2Bfor%2BThyroid%2BNodules%2Band%2BAutoimmune%2BThyroid%2BDiseases%2Bin%2BHiroshima%2Band%2BNagasaki%2BAtomic%2BBomb%2BSurvivors%2B55-58%2BYears%2BAfter%2BRadiation%2BExposure%26rft_id%253Dinfo%253Adoi%252F10.1001%252Fjama.295.9.1011%26rft_id%253Dinfo%253Apmid%252F16507802%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1001/jama.295.9.1011&link_type=DOI [3]: /lookup/external-ref?access_num=16507802&link_type=MED&atom=%2Fbmj%2F332%2F7541%2F597.atom [4]: /lookup/external-ref?access_num=000235656600021&link_type=ISI
Text-Book of Materia Medica for Nurses.
Journal: JAMA (1906)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Sleep now, pay later
Journal: JAMA (1969)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Peak oxygen consumption measurement differentiates physiological left ventricular hypertrophy in junior athletes from pathological hypertrophy in adolescents with hypertrophic cardiomyopathy Sanjay Sharma, Sami Firoozi, Brian Mist, Perry M. Elliott, Greg Whyte, William J. McKenna. St. George's Hospital Medical School, London, United Kingdom
Journal: Journal of the American College of Cardiology (2001)
Reply
Authors: Simone R.F.F. Pedra, Carlos A.C. Pedra, Alexandre A. Abizaid, Sérgio L.N. Braga, Rodolfo Staico, Raul Arrieta, J. Ribamar Costa, Vinicius D. Vaz, Valmir F. Fontes, J. Eduardo R. Sousa
Journal: Journal of the American College of Cardiology (2006)
Q&amp;A: Olufunmilayo Olopade on Genomics and Breast Cancer
Journal: Cancer Discovery (2020)

Olufunmilayo Olopade, MD, discusses her research on genomic sequencing and breast cancer, which has led to insights into how the disease progresses-and how it can be prevented. What's key, she says, is that one-size-fits-all screening shouldn't be recommended.
Safety and efficacy of high pressure retrograde cardiac venous injection. Implications for regional myocardial delivery Niall A. Herity, William Fearon, Bonnie L. Hiatt, Mehrdad Rezaee, Takeshi Suzuki, David P. Lee, Alan C. Yeung, Andrew J. Carter, Peter J. Fitzgerald, Paul G. Yock. Stanford University Medical Center, Stanford, CA
Journal: Journal of the American College of Cardiology (2001)
Table of Contents
Authors: F Cortiula, A Pettke, M Bartoletti, F Puglisi, T Helleday, M Van Dongen, M Kok, C Bosetti, C Santucci, S Gallus, M Martinetti, P Schmid, R Salgado, Y Park, E Muñoz-Couselo, S Kim, J Sohn, S.-A Im, T Foukakis, S Kuemmel, R Dent, L Yin, A Wang, K Tryfonidis, V Karantza, J Cortés, S Loi, S Adams, V Diéras, C Barrios, E Winer, A Schneeweiss, H Iwata, S Patel, V Henschel, S Chui, H Rugo, L Emens, A Waks, O Cohen, B Kochupurakkal, D Kim, C Dunn, J Buendia Buendia, S Wander, K Helvie, M Lloyd, L Marini, M Hughes, S Freeman, S Ivy, J Geradts, S Isakoff, P Lorusso, V Adalsteinsson, S Tolaney, U Matulonis, I Krop, A D'andrea, N Lin, G Shapiro, N Wagle, A Schoenfeld, H Rizvi, C Bandlamudi, J Sauter, W Travis, N Rekhtman, A Plodkowski, R Perez-Johnston, P Sawan, A Beras, J Egger, M Ladanyi, K Arbour, C Rudin, G Riely, B Taylor, M Donoghue, D Planchard, N Reinmuth, S Orlov, J Fischer, S Sugawara, S Mandziuk, D Marquez-Medina, S Novello, Y Takeda, R Soo, K Park, M Mccleod, S Geater, M Powell, R May, U Scheuring, P Stockman, D Kowalski, M Kolinsky, P Rescigno, D Bianchini, Z Zafeiriou, N Mehra, J Mateo, V Michalarea, R Riisnaes, M Crespo, I Figueiredo, S Miranda, D Nava Rodrigues, P Flohr, N Tunariu, U Banerji, R Ruddle, A Sharp, J Welti, M Lambros, S Carreira, F Raynaud, K Swales, S Plymate, J Luo, H Tovey, N Porta, R Slade, L Leonard, E Hall, J De Bono, J Tabernero, L Molife, J.-C Soria, A Cervantes, N Vogelzang, M Patel, M Hussain, A Baron, G Argilés, P Conkling, D Sampath, D Maslyar, P Patel, W Chan, S Gendreau, L Musib, N Xu, H Ma, K Lin, J Bendell, B Fu, M Song, X Li, J Han, H Adami, E Giovannucci, L Mucci
Journal: Annals of Oncology (2020)
JAMA Neurology
Journal: JAMA Neurology (2019)

The mission of JAMA Neurology is to publish scientifi c information primarily important for those physicians caring for people with neurologic disorders but also for those interested in the structure and function of the normal and diseased nervous system.These specifi c aims are (1) to make timely publication of original research of the nervous system, (2) to record observations of single patients or groups of patients that will provide new information and insights,(3) to report more basic research that is pertinent to the understanding of disease, (4) to introduce topics of practice, ethics, teaching, and history that are useful, and (5) to provide a forum for discussion on topics that may be controversial in this fi eld.This information will be published only after extensive peer review so that originality, clarity, and precision are ensured.
Vectorized Treg-depleting αCTLA-4 elicits antigen cross-presentation and CD8<sup>+</sup> T cell immunity to reject ‘cold’ tumors
Authors: Monika Semmrich, Jean-Baptiste Marchand, Laetitia Fend, Matilda Rehn, Christelle Remy, Petra Holmkvist, Nathalie Silvestre, Carolin Svensson, Patricia Kleinpeter, Jules Deforges, Fred Junghus, Kirstie L Cleary, Mimoza Bodén, Linda Mårtensson, Johann Foloppe, Ingrid Teige, Eric Quéméneur, Björn Frendéus
Journal: Journal for ImmunoTherapy of Cancer (2022)

Background Immune checkpoint blockade (ICB) is a clinically proven concept to treat cancer. Still, a majority of patients with cancer including those with poorly immune infiltrated ‘cold’ tumors are resistant to currently available ICB therapies. Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is one of few clinically validated targets for ICB, but toxicities linked to efficacy in approved αCTLA-4 regimens have restricted their use and precluded full therapeutic dosing. At a mechanistic level, accumulating preclinical and clinical data indicate dual mechanisms for αCTLA-4; ICB and regulatory T cell (Treg) depletion are both thought to contribute efficacy and toxicity in available, systemic, αCTLA-4 regimens. Accordingly, strategies to deliver highly effective, yet safe αCTLA-4 therapies have been lacking. Here we assess and identify spatially restricted exposure to a novel strongly Treg-depleting, checkpoint-blocking, vectorized αCTLA-4, as a highly efficacious and potentially safe strategy to target CTLA-4. Methods A novel human IgG1 CTLA-4 antibody (4-E03) was identified using function-first screening for monoclonal antibodies (mAbs) and targets associated with superior Treg-depleting activity. A tumor-selective oncolytic vaccinia vector was then engineered to encode this novel, strongly Treg-depleting, checkpoint-blocking, αCTLA-4 antibody or a matching surrogate antibody, and Granulocyte-macrophage colony-stimulating factor (GM-CSF) (VV GM -αCTLA-4). Results The identified 4-E03 antibody showed significantly stronger Treg depletion, but equipotent checkpoint blockade, compared with clinically validated αCTLA-4 ipilimumab against CTLA-4-expressing Treg cells in a humanized mouse model in vivo. Intratumoral administration of VV GM -αCTLA-4 achieved tumor-restricted CTLA-4 receptor saturation and Treg depletion, which elicited antigen cross-presentation and stronger systemic expansion of tumor-specific CD8 + T cells and antitumor immunity compared with systemic αCTLA-4 antibody therapy. Efficacy correlated with FcγR-mediated intratumoral Treg depletion. Remarkably, in a clinically relevant mouse model resistant to systemic ICB, intratumoral VV GM -αCTLA-4 synergized with αPD-1 to reject cold tumors. Conclusion Our findings demonstrate in vivo proof of concept for spatial restriction of Treg depletion-optimized immune checkpoint blocking, vectorized αCTLA-4 as a highly effective and safe strategy to target CTLA-4. A clinical trial evaluating intratumoral VV GM -αhCTLA-4 (BT-001) alone and in combination with αPD-1 in metastatic or advanced solid tumors has commenced.