{"id":"https://openalex.org/W7225737151","doi":"https://doi.org/10.3390/cells15222042","title":"From Early Activity to Phase III Program Attrition: The Anti-TIGIT Translation Gap","display_name":"From Early Activity to Phase III Program Attrition: The Anti-TIGIT Translation Gap","publication_year":2026,"publication_date":"2026-11-10","ids":{"openalex":"https://openalex.org/W7225737151","doi":"https://doi.org/10.3390/cells15222042"},"language":"en","primary_location":{"id":"doi:10.3390/cells15222042","doi":"https://doi.org/10.3390/cells15222042","is_oa":true,"landing_page_url":"https://doi.org/10.3390/cells15222042","pdf_url":null,"source":{"id":"https://openalex.org/S2736626452","display_name":"Cells","issn_l":"2073-4409","issn":["2073-4409"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","medline","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310310987","host_organization_name":"Multidisciplinary Digital Publishing Institute","host_organization_lineage":["https://openalex.org/P4310310987"],"host_organization_lineage_names":["Multidisciplinary Digital Publishing Institute"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Cells","raw_type":"journal-article"},"volume":null,"type":"article","is_traditional":true,"indexed_in":["crossref","doaj"],"open_access":{"is_oa":true,"oa_status":"gold","oa_url":"https://doi.org/10.3390/cells15222042","any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5075779667","display_name":"Alireza Tojjari","orcid":"https://orcid.org/0000-0002-2148-4425","observed_orcids":["https://orcid.org/0000-0002-2148-4425"]},"institutions":[{"id":"https://openalex.org/I4210128526","display_name":"UPMC Hillman Cancer Center","ror":"https://ror.org/03bw34a45","country_code":"US","type":"facility","lineage":["https://openalex.org/I170201317","https://openalex.org/I4210128526"]},{"id":"https://openalex.org/I4210134769","display_name":"University of Pittsburgh Medical Center","ror":"https://ror.org/04ehecz88","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I4210098814","https://openalex.org/I4210134769"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Alireza Tojjari","raw_affiliation_strings":["Department of Medicine, Division of Hematology & Medical Oncology, University of Pittsburgh Medical Center (UPMC), Pittsburgh, PA 15213, USA","UPMC Hillman Cancer Center, 5150 Centre Avenue, Pittsburgh, PA 15232, USA"],"raw_orcid":"https://orcid.org/0000-0002-2148-4425","affiliations":[{"raw_affiliation_string":"Department of Medicine, Division of Hematology & Medical Oncology, University of Pittsburgh Medical Center (UPMC), Pittsburgh, PA 15213, USA","institution_ids":["https://openalex.org/I4210134769"]},{"raw_affiliation_string":"UPMC Hillman Cancer Center, 5150 Centre Avenue, Pittsburgh, PA 15232, USA","institution_ids":["https://openalex.org/I4210128526","https://openalex.org/I4210134769"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5104877421","display_name":"Shamimeh Pourbahrighesmat","orcid":"https://orcid.org/0009-0004-6737-4880","observed_orcids":["https://orcid.org/0009-0004-6737-4880"]},"institutions":[{"id":"https://openalex.org/I4210128526","display_name":"UPMC Hillman Cancer Center","ror":"https://ror.org/03bw34a45","country_code":"US","type":"facility","lineage":["https://openalex.org/I170201317","https://openalex.org/I4210128526"]},{"id":"https://openalex.org/I4210134769","display_name":"University of Pittsburgh Medical Center","ror":"https://ror.org/04ehecz88","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I4210098814","https://openalex.org/I4210134769"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Shamimeh Pourbahrighesmat","raw_affiliation_strings":["Department of Medicine, Division of Hematology & Medical Oncology, University of Pittsburgh Medical Center (UPMC), Pittsburgh, PA 15213, USA","UPMC Hillman Cancer Center, 5150 Centre Avenue, Pittsburgh, PA 15232, USA"],"raw_orcid":"https://orcid.org/0009-0004-6737-4880","affiliations":[{"raw_affiliation_string":"Department of Medicine, Division of Hematology & Medical Oncology, University of Pittsburgh Medical Center (UPMC), Pittsburgh, PA 15213, USA","institution_ids":["https://openalex.org/I4210134769"]},{"raw_affiliation_string":"UPMC Hillman Cancer Center, 5150 Centre Avenue, Pittsburgh, PA 15232, USA","institution_ids":["https://openalex.org/I4210128526","https://openalex.org/I4210134769"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5048681236","display_name":"Anwaar Saeed","orcid":"https://orcid.org/0000-0001-8024-9401","observed_orcids":["https://orcid.org/0000-0001-8024-9401"]},"institutions":[{"id":"https://openalex.org/I4210128526","display_name":"UPMC Hillman Cancer Center","ror":"https://ror.org/03bw34a45","country_code":"US","type":"facility","lineage":["https://openalex.org/I170201317","https://openalex.org/I4210128526"]},{"id":"https://openalex.org/I4210134769","display_name":"University of Pittsburgh Medical Center","ror":"https://ror.org/04ehecz88","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I4210098814","https://openalex.org/I4210134769"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Anwaar Saeed","raw_affiliation_strings":["Department of Medicine, Division of Hematology & Medical Oncology, University of Pittsburgh Medical Center (UPMC), Pittsburgh, PA 15213, USA","UPMC Hillman Cancer Center, 5150 Centre Avenue, Pittsburgh, PA 15232, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Medicine, Division of Hematology & Medical Oncology, University of Pittsburgh Medical Center (UPMC), Pittsburgh, PA 15213, USA","institution_ids":["https://openalex.org/I4210134769"]},{"raw_affiliation_string":"UPMC Hillman Cancer Center, 5150 Centre Avenue, Pittsburgh, PA 15232, USA","institution_ids":["https://openalex.org/I4210128526","https://openalex.org/I4210134769"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":2,"corresponding_author_ids":["https://openalex.org/A5048681236"],"corresponding_institution_ids":["https://openalex.org/I4210128526","https://openalex.org/I4210134769"],"apc_list":{"value":2700,"currency":"CHF","value_usd":3258},"apc_paid":{"value":2700,"currency":"CHF","value_usd":3258},"fwci":0.0,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":{"value":0.0,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":null,"biblio":{"volume":"15","issue":"22","first_page":"2042","last_page":"2042"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10158","display_name":"Cancer Immunotherapy and Biomarkers","score":0.9994999766349792,"subfield":{"id":"https://openalex.org/subfields/2730","display_name":"Oncology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T10158","display_name":"Cancer Immunotherapy and Biomarkers","score":0.9994999766349792,"subfield":{"id":"https://openalex.org/subfields/2730","display_name":"Oncology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10031","display_name":"T-cell and B-cell Immunology","score":9.999999747378752e-05,"subfield":{"id":"https://openalex.org/subfields/2403","display_name":"Immunology"},"field":{"id":"https://openalex.org/fields/24","display_name":"Immunology and Microbiology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10580","display_name":"Immunotherapy and Immune Responses","score":9.999999747378752e-05,"subfield":{"id":"https://openalex.org/subfields/2403","display_name":"Immunology"},"field":{"id":"https://openalex.org/fields/24","display_name":"Immunology and Microbiology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[],"concepts":[{"id":"https://openalex.org/C203092338","wikidata":"https://www.wikidata.org/wiki/Q1340863","display_name":"Clinical endpoint","level":3,"score":0.5946000218391418},{"id":"https://openalex.org/C2781197716","wikidata":"https://www.wikidata.org/wiki/Q864574","display_name":"Biomarker","level":2,"score":0.47850000858306885},{"id":"https://openalex.org/C535046627","wikidata":"https://www.wikidata.org/wiki/Q30612","display_name":"Clinical trial","level":2,"score":0.46939998865127563},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.4262000024318695},{"id":"https://openalex.org/C2777701055","wikidata":"https://www.wikidata.org/wiki/Q1427096","display_name":"Immunotherapy","level":3,"score":0.40529999136924744},{"id":"https://openalex.org/C31760486","wikidata":"https://www.wikidata.org/wiki/Q7180990","display_name":"Phases of clinical research","level":3,"score":0.3950999975204468},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.3698999881744385},{"id":"https://openalex.org/C143998085","wikidata":"https://www.wikidata.org/wiki/Q162555","display_name":"Oncology","level":1,"score":0.3569999933242798},{"id":"https://openalex.org/C2781413609","wikidata":"https://www.wikidata.org/wiki/Q7308373","display_name":"Regimen","level":2,"score":0.3474000096321106},{"id":"https://openalex.org/C149364088","wikidata":"https://www.wikidata.org/wiki/Q185917","display_name":"Translation (biology)","level":4,"score":0.34459999203681946},{"id":"https://openalex.org/C60644358","wikidata":"https://www.wikidata.org/wiki/Q128570","display_name":"Bioinformatics","level":1,"score":0.337799996137619},{"id":"https://openalex.org/C141341695","wikidata":"https://www.wikidata.org/wiki/Q2368661","display_name":"Surrogate endpoint","level":2,"score":0.3068999946117401},{"id":"https://openalex.org/C2779134260","wikidata":"https://www.wikidata.org/wiki/Q12136","display_name":"Disease","level":2,"score":0.2847000062465668},{"id":"https://openalex.org/C2992264114","wikidata":"https://www.wikidata.org/wiki/Q1394551","display_name":"Clinical disease","level":3,"score":0.2808000147342682},{"id":"https://openalex.org/C44280652","wikidata":"https://www.wikidata.org/wiki/Q104837","display_name":"Phase (matter)","level":2,"score":0.27970001101493835},{"id":"https://openalex.org/C41008148","wikidata":"https://www.wikidata.org/wiki/Q21198","display_name":"Computer science","level":0,"score":0.2770000100135803},{"id":"https://openalex.org/C10515644","wikidata":"https://www.wikidata.org/wiki/Q543310","display_name":"Survival analysis","level":2,"score":0.27300000190734863},{"id":"https://openalex.org/C15744967","wikidata":"https://www.wikidata.org/wiki/Q9418","display_name":"Psychology","level":0,"score":0.2621999979019165},{"id":"https://openalex.org/C81917197","wikidata":"https://www.wikidata.org/wiki/Q628760","display_name":"Selection (genetic algorithm)","level":2,"score":0.25949999690055847},{"id":"https://openalex.org/C168563851","wikidata":"https://www.wikidata.org/wiki/Q1436668","display_name":"Randomized controlled trial","level":2,"score":0.25870001316070557}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.3390/cells15222042","doi":"https://doi.org/10.3390/cells15222042","is_oa":true,"landing_page_url":"https://doi.org/10.3390/cells15222042","pdf_url":null,"source":{"id":"https://openalex.org/S2736626452","display_name":"Cells","issn_l":"2073-4409","issn":["2073-4409"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","medline","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310310987","host_organization_name":"Multidisciplinary Digital Publishing Institute","host_organization_lineage":["https://openalex.org/P4310310987"],"host_organization_lineage_names":["Multidisciplinary Digital Publishing Institute"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Cells","raw_type":"journal-article"}],"best_oa_location":{"id":"doi:10.3390/cells15222042","doi":"https://doi.org/10.3390/cells15222042","is_oa":true,"landing_page_url":"https://doi.org/10.3390/cells15222042","pdf_url":null,"source":{"id":"https://openalex.org/S2736626452","display_name":"Cells","issn_l":"2073-4409","issn":["2073-4409"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","medline","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310310987","host_organization_name":"Multidisciplinary Digital Publishing Institute","host_organization_lineage":["https://openalex.org/P4310310987"],"host_organization_lineage_names":["Multidisciplinary Digital Publishing Institute"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Cells","raw_type":"journal-article"},"sustainable_development_goals":[],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":34,"referenced_works":["https://openalex.org/W2029399624","https://openalex.org/W2624831627","https://openalex.org/W2808202038","https://openalex.org/W2808601843","https://openalex.org/W2884397450","https://openalex.org/W2965242861","https://openalex.org/W2973224612","https://openalex.org/W3025022288","https://openalex.org/W3093283515","https://openalex.org/W3138484572","https://openalex.org/W3171517418","https://openalex.org/W4220788548","https://openalex.org/W4280554695","https://openalex.org/W4361217001","https://openalex.org/W4385996375","https://openalex.org/W4388753162","https://openalex.org/W4390945535","https://openalex.org/W4392242507","https://openalex.org/W4394934050","https://openalex.org/W4402565599","https://openalex.org/W4405419500","https://openalex.org/W4406641209","https://openalex.org/W4415310942","https://openalex.org/W4416391616","https://openalex.org/W7116968447","https://openalex.org/W7128589180","https://openalex.org/W7128775802","https://openalex.org/W7159082948","https://openalex.org/W7168298410","https://openalex.org/W7168765332","https://openalex.org/W7171355843","https://openalex.org/W7197031062","https://openalex.org/W7203914871","https://openalex.org/W7223041434"],"related_works":[],"abstract_inverted_index":{"T-cell":[0],"immunoreceptor":[1,5],"with":[2],"immunoglobulin":[3],"and":[4,38,79,101,162],"tyrosine-based":[6],"inhibitory":[7],"motif":[8],"domains":[9],"(TIGIT)":[10],"has":[11],"a":[12,17,85,119],"compelling":[13],"biological":[14,91],"rationale":[15],"as":[16],"partner":[18],"for":[19,149],"programmed":[20,26],"cell":[21],"death":[22],"protein":[23],"1":[24,28],"or":[25,66],"death-ligand":[27],"blockade.":[29],"Early":[30],"clinical":[31,59,155],"activity":[32],"supported":[33],"development":[34,170],"in":[35],"lung,":[36],"hepatocellular,":[37],"gastroesophageal":[39],"cancers,":[40],"but":[41],"randomized":[42],"studies":[43],"have":[44],"not":[45,89,177],"established":[46,178],"broadly":[47],"reproducible":[48],"incremental":[49],"benefit":[50],"over":[51],"contemporary":[52],"immunotherapy":[53],"backbones.":[54],"This":[55],"Perspective":[56],"distinguishes":[57],"observed":[58],"outcomes":[60],"from":[61,64],"explanations":[62,106],"inferred":[63],"experimental":[65],"exploratory":[67],"translational":[68],"studies.":[69],"Small":[70],"early":[71],"trials,":[72],"subgroup":[73],"selection,":[74],"nonidentical":[75],"controls,":[76],"endpoint":[77,87],"maturity,":[78],"multiplicity":[80],"complicate":[81],"interpretation;":[82],"failure":[83,134],"of":[84,111,118,135],"prespecified":[86],"does":[88],"prove":[90],"inactivity.":[92],"CD226":[93],"dysfunction,":[94],"immune-cell":[95],"state,":[96],"Fc-dependent":[97],"effects,":[98],"backbone":[99],"redundancy,":[100],"adaptive":[102],"resistance":[103],"remain":[104],"candidate":[105],"rather":[107],"than":[108],"demonstrated":[109],"causes":[110],"phase":[112],"III":[113],"failure.":[114],"SKYSCRAPER-08":[115],"establishes":[116],"efficacy":[117],"TIGIT-containing":[120],"regimen":[121],"without":[122],"isolating":[123],"its":[124],"TIGIT":[125],"component,":[126],"whereas":[127],"subsequent":[128],"SKYSCRAPER-07":[129],"comparisons":[130],"are":[131,172],"descriptive":[132],"after":[133],"hierarchical":[136],"testing.":[137],"The":[138],"belrestotug":[139],"program":[140],"further":[141],"illustrates":[142],"why":[143],"improved":[144],"response":[145],"alone":[146],"is":[147],"insufficient":[148],"advancement.":[150],"We":[151],"propose":[152],"prospectively":[153],"specified":[154],"precision":[156],"requirements,":[157],"mechanism-linked":[158],"intratumoral":[159],"pharmacodynamic":[160],"activity,":[161],"practical":[163],"biomarker":[164],"validation":[165],"before":[166],"confirmatory":[167],"expansion.":[168],"These":[169],"criteria":[171],"proposals":[173],"requiring":[174],"prospective":[175],"evaluation,":[176],"selection":[179],"rules.":[180]},"counts_by_year":[],"updated_date":"2026-11-11T12:16:26.678958","created_date":"2026-11-11T00:00:00"}