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During a series of presentations of scientific papers 40.6% of 276 subjects reported dreaming, but only 18.1% actually fell asleep. The frequency of dreaming was significantly increased by the addition of either "very boring" or "very interesting" slides to the usual ones, but not by "neutral" slides. The recall of lecture content and the proportion of audience asleep were (surprisingly) not greatly affected by the addition of extraneous slides of any sort. On the other hand, adding "very interesting" slides greatly increases audience enjoyment. [ABSTRACT FROM PUBLISHER]

Background: Afamitresgene autoleucel (afami-cel) showed acceptable safety and promising efficacy in a phase 1 trial (NCT03132922). The aim of this study was to further evaluate the efficacy of afami-cel for the treatment of patients with HLA-A*02 and MAGE-A4-expressing advanced synovial sarcoma or myxoid round cell liposarcoma., Methods: SPEARHEAD-1 was an open-label, non-randomised, phase 2 trial done across 23 sites in Canada, the USA, and Europe. The trial included three cohorts, of which the main investigational cohort (cohort 1) is reported here. Cohort 1 included patients with HLA-A*02, aged 16-75 years, with metastatic or unresectable synovial sarcoma or myxoid round cell liposarcoma (confirmed by cytogenetics) expressing MAGE-A4, and who had received at least one previous line of anthracycline-containing or ifosfamide-containing chemotherapy. Patients received a single intravenous dose of afami-cel (transduced dose range 1·0 × 10 9 -10·0 × 10 9 T cells) after lymphodepletion. The primary endpoint was overall response rate in cohort 1, assessed by a masked independent review committee using Response Evaluation Criteria in Solid Tumours (version 1.1) in the modified intention-to-treat population (all patients who received afami-cel). Adverse events, including those of special interest (cytokine release syndrome, prolonged cytopenia, and neurotoxicity), were monitored and are reported for the modified intention-to-treat population. This trial is registered at ClinicalTrials.gov, NCT04044768; recruitment is closed and follow-up is ongoing for cohorts 1 and 2, and recruitment is open for cohort 3., Findings: Between Dec 17, 2019, and July 27, 2021, 52 patients with cytogenetically confirmed synovial sarcoma (n=44) and myxoid round cell liposarcoma (n=8) were enrolled and received afami-cel in cohort 1. Patients were heavily pre-treated (median three [IQR two to four] previous lines of systemic therapy). Median follow-up time was 32·6 months (IQR 29·4-36·1). Overall response rate was 37% (19 of 52; 95% CI 24-51) overall, 39% (17 of 44; 24-55) for patients with synovial sarcoma, and 25% (two of eight; 3-65) for patients with myxoid round cell liposarcoma. Cytokine release syndrome occurred in 37 (71%) of 52 of patients (one grade 3 event). Cytopenias were the most common grade 3 or worse adverse events (lymphopenia in 50 [96%], neutropenia 44 [85%], leukopenia 42 [81%] of 52 patients). No treatment-related deaths occurred., Interpretation: Afami-cel treatment resulted in durable responses in heavily pre-treated patients with HLA-A*02 and MAGE-A4-expressing synovial sarcoma. This study shows that T-cell receptor therapy can be used to effectively target solid tumours and provides rationale to expand this approach to other solid malignancies., Funding: Adaptimmune., Competing Interests: Declaration of interests EC reports participation in an advisory board for Adaptimmune; and research support paid to their institution for clinical trial activities from Adaptimmune, Novartis, Tracon, Boehringer Ingelheim, Merck, Bayer, Amgen, and Mirati. J-YB reports grants paid to institution from Netsarc+ and Euracan; and research support and honoraria from Adaptimmune and GSK. FT reports research support paid to institution for clinical trial activities from Adaptimmune, Achilles Therapeutics, T-knife Therapeutics, GSK, Immunocore, and Instil Bio; consulting fees from T-knife Therapeutics; speaker fees from Kite and Royal Marsden Hospital Cell Therapy Preceptorship; travel or meeting support from Kite; advisory board fees from Immatics, Bristol Myers Squibb (BMS), GSK, Janssen, Leucid, and Scenic Biotech; institutional advisory board fees from Pfizer; and is an unpaid panel member with Sarcoma UK, Cancer Research UK New Agents Committee, and the Medical Research Council Developmental pathway funding scheme. MA reports institutional support from Exelixis; consulting fees from Boehringer Ingelheim and Aadi; and honoraria from Regeneron, Deciphera, and Bayer. EF reports honoraria from Novartis, Alexion, Astellas, GSK, Gilead, and Sanofi; and travel or meeting support from Novartis, Alexion, Gilead, Sanofi, MSD, and Neovii. SJS reports consulting fees from Ceridwen Oncology; honoraria from Boehringer Ingelheim; travel or meeting support from Adaptimmune; and participated on advisory or data safety monitoring boards for GSK and Inhibrx. ARAR reports support from Adaptimmune, AbbVie, Amgen, Blueprint Medicines, BMS, Daiichi Sankyo, Deciphera Pharmaceuticals, GSK, Iterion Therapeutics, Karyopharm Therpaeutics, MedImmune, Merck, Neoleuki Therapeutics, Pfizer, Rain Therapeutics, Roche/Genentech, and Symphogen; honoraria from Medison; and participated on advisory or data safety monitoring boards for Adaptimmune, Bayer, GSK, Inhibrx, and Medison. SMS reports institutional support from Adaptimmune, Boehringer Ingelheim, GSK, Rain Oncology, Shanghai Pharma, and TRACON; royalties or licenses from UpToDate; participated on an advisory or data safety monitoring board for Bioatla; and is an unpaid National Comprehensive Cancer Network Soft Tissue Sarcoma committee member. CMVM reports institutional support from Adaptimmune; consulting fees from Deciphera; honoraria from Bayer; travel or meeting support from PharmaMar; and participation on advisory or data safety monitoring boards for PharmaMar, Bayer, and Boehringer Ingelheim. MJW reports consulting fees from Adaptimmune, Deciphera, Aadi, Epizyme, and PharmaEssentia. JG reports support from Adaptimmune for this study. VM reports consulting fees from Roche, Bayer, Pieris, BMS, Janssen, Basilea, Regeneron/Sanofi, and Nanobiotix; and institutional support from AbbVie, AceaBio, Adaptimmune, ADC Therapeutics, Aduro, Agenus, Amcure, Amgen, Astellas, AstraZeneca, Bayer, Beigene, BioInvent International, BMS, Boehringer Ingelheim, Boston, Celgene, Daiichi Sankyo, Debiopharm, Eisai, e-Therapeutics, Exelisis, Forma Therapeutics, Genmab, GSK, Harpoon, Hutchison, Immutep, Incyte, Inovio, Iovance, Janssen, Kyowa Kirin, Lilly, Loxo, MedSir, Menarini, Merck, Merus, Millenium, MSD, Nanobiotix, Nektar, Novartis, Odonate Therapeutics, Pfizer, PharmaMar, Pricipia, PsiOxus, Puma, Regeneron, Rigontec, Roche, Sanofi, Sierra Oncology, Synthon, Taiho, Takeda, Tesaro, Transgene, Turning Point Therapeutics, and Upsher-Smith. LH, TW, JB, AS, LF, EVW, EN, DW, RW, J-MN, SR, and EE are employees of, and have stock options in, Adaptimmune. SB, CM, and CL were employees of Adaptimmune at the time of the study. VLK reports institutional support from Adaptimmune, Deciphera, Plexxikon, Advenchen, Boehringer Ingelheim, and TRACON; consulting fees from Epizyme; and honoraria from Deciphera. WDT reports institutional support from Adaptimmune; consulting and travel fees from Eli Lilly; consulting fees from C4 Therapeutics, Daiichi Sankyo, Deciphera, Adcendo, Ayala Pharmaceuticals, Kowa, Servier, Bayer Pharmaceuticals, Epizyme, Cogent, Medpacto, Foghorn Therapeutics, Amgen, AmMax Bio, Boehringer Ingelheim, BioAtla, Inhibrx, PharmaEssentia, Avacta, Ipsen, Sonata, Curadev, Nuvation Bio, and Abbisko; has patents pending for companion diagnostics with Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center (New York, NY, USA); is on advisory boards of Innova Therapeutics and the Osteosarcoma Institute; is on the advisory board and holds stock in Certis Oncology Solutions; and is a co-founder and has stock in Atropos Therapeutics. JAC reports consulting fees from Adaptimmune and Deciphera; and honoraria from Adaptimmune. BAVT reports a research grant from Polaris; royalties or licenses from Accuronix Therapeutics; consulting fees from Bayer, Deciphera, GIST Expert Interview Project, Daiichi Sankyo, EcoR1, Advenchen, Putnam, Salarius Pharmaceuticals, Boxer Capital, Acuta Capital Partners, Aadi, Race Oncology, Hinge Bio, Kronos Bio, and Sonata Therapeutics; honoraria from Total Health Conference and Iterion Therapeutics; travel or meeting support from Adaptimmune, Kronos Bio, Advenchen Laboratories, and Polaris; has a patent with Accuronix Therapeutics; participated in advisory boards for Apexigen, Daiichi Sankyo, Epizyme, Bayer, PTC Therapeutics, Aadi Biosciences, Boehringer Ingelheim, Agenus, Regeneron Pharmaceuticals, Exp, Advenchen, EcoR1 Capital, Curis, and Inhibrx; and is a board member for Polaris. GDD reports institutional support from Adaptimmune, Bayer, Novartis, PharmaMar, and Daiichi-Sankyo; is a co-founder and scientific advisory board member with minor equity holding in IDRx; is a consultant or scientific advisory board member with minor equity holding in G1 Therapeutics, Caris Life Sciences, Erasca Pharmaceuticals, RELAY Therapeutics, Bessor Pharmaceuticals, CellCarta, Ikena Oncology, Kojin Therapeutics, Aadi Biosciences, Acrivon Therapeutics, Blueprint Medicines, Tessellate Bio, and Boundless Bio; and is a scientific consultant for EMD-Serono/Merck KGaA, WCG/Arsenal Capital, Rain Therapeutics, and Minghui Pharmaceuticals. SPD'A reports institutional support from Adaptimmune for this study; grants, contracts, consulting fees, and honoraria from EMD Serono, Amgen, Nektar, Immune Design, GlaxoSmithKline, Incyte, Merck, Adaptimmune, Immunocore, Pfizer, Servier, Rain Therapeutics, GI Innovations, and Aadi Biosciences; travel support from Adaptimmune, EMD Serono, and Nektar; participation on advisory boards for GlaxoSmithKline, Nektar, Adaptimmune, and Merck; and a leadership or fiduciary role at the Connective Tissue Oncology Society in 2023–24. SA reports institutional support from Adaptimmune for this study; and institutional support from TRACON Pharma, Ayala Pharmaceuticals, Cogent Biosciences, InhibRx, Rain Therapeutics, Trillium Therapeutics, Boehringer Ingelheim, Salarius Pharmaceuticals, Theseus Pharmaceuticals, Monopar Therapeutics, C4 Therapeutics, Noxopharm, Jazz Pharmaceuticals, Shanghai Pharma, and PharmaMar. KNG reports participation in advisory boards for Adaptimmune, Daiichi Sankyo, Boehringer Ingelheim, and Deciphera. MD reports consultancy fees and advisory board fees from Deciphera, Aadi Bioscience, and Daiichi Sankyo. BAW reports consultancy fees from Springworks, Deciphera, Epizyme, Adcendo, Polaris, Boehringer Ingelheim, and AADi, research funding from Exelixis, and travel support from Agenus. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Affinity-optimized T cell receptors can enhance the potency of adoptive T cell therapy. Afamitresgene autoleucel (afami-cel) is a human leukocyte antigen-restricted autologous T cell therapy targeting melanoma-associated antigen A4 (MAGE-A4), a cancer/testis antigen expressed at varying levels in multiple solid tumors. We conducted a multicenter, dose-escalation, phase 1 trial in patients with relapsed/refractory metastatic solid tumors expressing MAGE-A4, including synovial sarcoma (SS), ovarian cancer and head and neck cancer ( NCT03132922 ). The primary endpoint was safety, and the secondary efficacy endpoints included overall response rate (ORR) and duration of response. All patients (N = 38, nine tumor types) experienced Grade ≥3 hematologic toxicities; 55% of patients (90% Grade ≤2) experienced cytokine release syndrome. ORR (all partial response) was 24% (9/38), 7/16 (44%) for SS and 2/22 (9%) for all other cancers. Median duration of response was 25.6 weeks (95% confidence interval (CI): 12.286, not reached) and 28.1 weeks (95% CI: 12.286, not reached) overall and for SS, respectively. Exploratory analyses showed that afami-cel infiltrates tumors, has an interferon-γ-driven mechanism of action and triggers adaptive immune responses. In addition, afami-cel has an acceptable benefit-risk profile, with early and durable responses, especially in patients with metastatic SS. Although the small trial size limits conclusions that can be drawn, the results warrant further testing in larger studies., (© 2023. The Author(s).)

We evaluated the safety and activity of autologous T cells expressing NY-ESO-1 c259 , an affinity-enhanced T-cell receptor (TCR) recognizing an HLA-A2-restricted NY-ESO-1/LAGE1a-derived peptide, in patients with metastatic synovial sarcoma (NY-ESO-1 c259 T cells). Confirmed antitumor responses occurred in 50% of patients (6/12) and were characterized by tumor shrinkage over several months. Circulating NY-ESO-1 c259 T cells were present postinfusion in all patients and persisted for at least 6 months in all responders. Most of the infused NY-ESO-1 c259 T cells exhibited an effector memory phenotype following ex vivo expansion, but the persisting pools comprised largely central memory and stem-cell memory subsets, which remained polyfunctional and showed no evidence of T-cell exhaustion despite persistent tumor burdens. Next-generation sequencing of endogenous TCRs in CD8 + NY-ESO-1 c259 T cells revealed clonal diversity without contraction over time. These data suggest that regenerative pools of NY-ESO-1 c259 T cells produced a continuing supply of effector cells to mediate sustained, clinically meaningful antitumor effects. Significance: Metastatic synovial sarcoma is incurable with standard therapy. We employed engineered T cells targeting NY-ESO-1, and the data suggest that robust, self-regenerating pools of CD8 + NY-ESO-1 c259 T cells produce a continuing supply of effector cells over several months that mediate clinically meaningful antitumor effects despite prolonged exposure to antigen. Cancer Discov; 8(8); 944-57. ©2018 AACR. See related commentary by Keung and Tawbi, p. 914 This article is highlighted in the In This Issue feature, p. 899 ., (©2018 American Association for Cancer Research.)

Background: The positive predictive value (PPV) of conventional preschool acuity screening is about 50% whereas previous Polaroid photoscreening with experienced interpretation can achieve PPV greater than 85%. The Plusoptix photoscreener has immediate computer interpretation and a CPT code available to pediatricians., Methods: Two Plusoptix SO9 were used in two pediatric group practices with previously validated refractive criteria and new manufacturer's binocular alignment criteria. CPT billing was monitored. Referred patients had prior gold-standard AAPOS examinations., Results: 12% of 675 photoscreened preschoolers were referred. Of the 39 with AAPOS gold-standard exams, the PPV from strabismus referrals was 17%, while 26 of 27 refractive referrals had true amblyopia risk factors (PPV 96%). Screening CPT code 99174 reimbursement rose from zero to half of insurers in 15 months., Conclusion: Plusoptix photoscreening is valid after adjusting the binocular alignment criteria. Such photoscreening should be employed by pediatric practices to detect and ultimately to reduce amblyopia vision impairment in children.

Purpose: To determine the (1) incidence of peripheral blood glucose (PBG < 40 mg/dL) in infants within 2 hours of birth and (2) validity of using maternal and infant risk factors and/or infant signs/symptoms of hypoglycemia as a screen for PBG < 40 mg/dL., Study Design: Descriptive study with a convenience sample of 220 mother-infant dyads admitted to a mother-baby unit. Maternal and infant risk factors and infant signs/symptoms of hypoglycemia were assessed, and a PBG value was obtained within 2 hours of birth from the infant. Data were analyzed with descriptive statistics, multiple regression analysis, and sensitivity and specificity testing., Results: The incidence of PBG < 40 mg/dL was 5.1% (N = 10 of 198). Fifteen maternal/infant risk factors were found; 2 of the 23 risk factors predicted PBG values within 2 hours of birth at a statistically significant level (jitteriness [p = .011] and tachypnea [p = .033]). Sensitivity was 71.9% and specificity 44.7% for using the presence of at least one maternal/infant risk factor and/or infant signs/symptoms of hypoglycemia to correctly identify PBG < 40 mg/dL within 2 hours of birth., Clinical Implications: Nurses working with mothers and infants can use the data from our study along with the recommendations from professional organizations such as American Academy of Pediatrics to begin a conversation at their institutions about revising protocols for routine PBG testing. Screening infants for maternal/infant risk factors and infant signs/symptoms of hypoglycemia could be used instead to safely decrease by 45% the number of infants who would need to have a PBG sample obtained within 2 hours of birth.