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"sequence_sha256": "8bc781a703ce6e2649f88d9263abc8327cf5e4a4846edf5103d0dde5d4a0a802", "start_1based": 157 } ] }, { "symbol": "CTAG2", "gene_id": "ENSG00000126890", "peptide": "SLLMWITQC", "isoform_scope": "LAGE-1A 157-165; no transfer to LAGE-1B or other CTAG2 peptides", "sequence_reference": "Ensembl 115 / GRCh38", "sequence_matches": [ { "protein_id": "ENSP00000358598.3", "length": 180, "sequence_sha256": "5608df0b33405188339c7831de55351f60eda47a1002ae5ea1ef320c9738106b", "start_1based": 157 } ] } ], "identity_sources": [ "tbi1301_2022" ], "review_scope": "Published nine-person cohort; unresolved grade 3 lung-injury mechanism prevents favorable credit." }, { "product_id": "magea3_a2_neuro", "name": "NCI HLA-A*02-restricted MAGE-A3/A9/A12-reactive TCR", "modality": "TCR-T", "taxon_id": 9606, "hla": [ "HLA-A*02:01" ], "targets": [ { "symbol": "MAGEA3", "gene_id": "ENSG00000221867", "peptide": "KVAELVHFL", "isoform_scope": "Shared intended peptide", "sequence_reference": "Ensembl 115 / 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"0bc7ebd4e1561184c6891757f9ef2d0843d5022016750fd5cb092a25baad51a2", "start_1based": 111 } ] }, { "symbol": "MAGEA12", "gene_id": "ENSG00000213401", "peptide": "KMAELVHFL", "isoform_scope": "Cross-recognized variant peptide; suspected normal brain source", "sequence_reference": "Ensembl 115 / GRCh38", "sequence_matches": [ { "protein_id": "ENSP00000377447.3", "length": 314, "sequence_sha256": "0109d7827258db081cc89240a49da2500deec2eff44b1896903344e0075a54be", "start_1based": 112 }, { "protein_id": "ENSP00000350592.4", "length": 314, "sequence_sha256": "0109d7827258db081cc89240a49da2500deec2eff44b1896903344e0075a54be", "start_1based": 112 }, { "protein_id": "ENSP00000377478.3", "length": 314, "sequence_sha256": "0109d7827258db081cc89240a49da2500deec2eff44b1896903344e0075a54be", "start_1based": 112 }, { "protein_id": "ENSP00000586307.1", "length": 314, "sequence_sha256": "0109d7827258db081cc89240a49da2500deec2eff44b1896903344e0075a54be", "start_1based": 112 } ] }, { "symbol": "MAGEA9B", "gene_id": "ENSG00000267978", "peptide": "KVAELVHFL", "isoform_scope": "Reference-verified shared peptide; MAGE-A9 protein-identical partner, not separately attributed clinical expression", "sequence_reference": "Ensembl 115 / GRCh38", "sequence_matches": [ { "protein_id": "ENSP00000471017.1", "length": 315, "sequence_sha256": "0bc7ebd4e1561184c6891757f9ef2d0843d5022016750fd5cb092a25baad51a2", "start_1based": 111 }, { "protein_id": "ENSP00000472733.1", "length": 195, "sequence_sha256": "bc4feda2bf50320586fa625b7be05400ba24bcd837c2fe7d81fc4eb91c4af78e", "start_1based": 111 }, { "protein_id": "ENSP00000620192.1", "length": 315, "sequence_sha256": "0bc7ebd4e1561184c6891757f9ef2d0843d5022016750fd5cb092a25baad51a2", "start_1based": 111 } ] } ], "identity_sources": [ "magea3_neuro_2013" ], "review_scope": "Primary abstract and indexed full-text epitope/mechanism passages; normal neuronal antigen attribution remains proposed." } ], "cohorts": [ { "cohort_id": "lete_mrcls_20", "product_id": "lete_cel_c259", "trial_ids": [ "NCT02992743" ], "patients_treated": 20, "population": "Advanced/metastatic myxoid/round cell liposarcoma", "source": "lete_mrcls_2025", "source_sections": "Results: Patients; Safety; Discussion", "review_status": "reviewed", "grade45_specificity": "none_identified", "follow_up": "Safety cutoff May 2022; survival follow-up January 2023. A fatal cardiac event occurred on day 161.", "overlap_note": "Two sequential 10-person cohorts counted once; repeat infusion does not add a patient.", "finding": "No grade 4-5 event was attributed to peptide-specific recognition of normal tissue. Grade 4 cytopenias occurred; one late cardiac death remained potentially treatment-related without an established specificity mechanism.", "qualification": "This is a curation conclusion about reported attribution, not an author-reported zero-event rate or proof of safety.", "trial_registration_urls": [ "https://clinicaltrials.gov/study/NCT02992743" ] }, { "cohort_id": "ima203_phase1_40", "product_id": "ima203", "trial_ids": [ "NCT03686124" ], "patients_treated": 40, "population": "PRAME-positive advanced solid tumors", "source": "ima203_2025", "source_sections": "Results: Safety; preclinical specificity; Methods: Statistical analysis", "review_status": "reviewed", "grade45_specificity": "none_identified", "follow_up": "Interim cutoff July 4, 2023; phase 1a and phase 1b monotherapy.", "overlap_note": "40 infused, 41 started lymphodepletion. Do not count the pre-infusion death as TCR exposure.", "finding": "No treatment-related deaths after IMA203 infusion were reported. Severe cytopenias and CRS occurred; no clinical renal toxicity was seen despite weak reactivity in one in-vitro renal donor.", "qualification": "Normal peptide non-detection is assay-limited; this does not clear all PRAME peptides.", "trial_registration_urls": [ "https://clinicaltrials.gov/study/NCT03686124" ] }, { "cohort_id": "afami_phase1_38", "product_id": "afami_cel_c1032", "trial_ids": [ "NCT03132922" ], "patients_treated": 38, "population": "MAGE-A4-positive advanced solid tumors", "source": "afami_phase1_2023", "source_sections": "Results: Safety; Discussion", "review_status": "reviewed", "grade45_specificity": "none_identified", "follow_up": "Published phase 1 analysis; fatal events at days 17 and 55.", "overlap_note": "Separate patients from SPEARHEAD-1 cohort 1.", "finding": "Two possibly treatment-related deaths occurred: aplastic anemia and ischemic stroke. Marrow evaluation did not support MAGE-A4-directed injury; high-dose conditioning and inflammation were considered contributors.", "qualification": "The fatal stroke has no demonstrated specificity mechanism; neither death is relabelled unrelated.", "trial_registration_urls": [ "https://clinicaltrials.gov/study/NCT03132922" ] }, { "cohort_id": "spearhead1_cohort1_52", "product_id": "afami_cel_c1032", "trial_ids": [ "NCT04044768" ], "patients_treated": 52, "population": "Synovial sarcoma or myxoid/round cell liposarcoma", "source": "spearhead1_2024", "source_sections": "Results: Safety; Table 2; Discussion", "review_status": "reviewed", "grade45_specificity": "none_identified", "follow_up": "Published cohort 1 analysis; later cohorts are outside this snapshot.", "overlap_note": "One 52-person cohort, not independent counts per indication or subsequent publication.", "finding": "No grade 5 adverse events or treatment-related deaths were reported; severe cytopenias and mostly low-grade CRS remained important regimen toxicities.", "qualification": "No identified specificity event in this selected cohort does not establish a population-wide zero risk.", "trial_registration_urls": [ "https://clinicaltrials.gov/study/NCT04044768" ] }, { "cohort_id": "magea3_a3a_two_cases", "product_id": "magea3_a3a", "trial_ids": [ "NCT01350401", "NCT01352286" ], "patients_treated": 2, "population": "One melanoma and one multiple myeloma patient", "source": "magea3_titin_2013", "source_sections": "Abstract; Results: Post-clinical investigations; Discussion", "review_status": "reviewed", "grade45_specificity": "suspected_or_confirmed", "follow_up": "Fatal cardiac injury within 4-5 days of infusion.", "overlap_note": "The two patients described in linked clinical and mechanistic reports are counted once.", "finding": "Fatal cardiac injury was attributed to T-cell cross-recognition, with titin identified as the likely unintended antigen.", "qualification": "The finding blocks credit for this receptor; it does not prove that MAGE-A3 protein was present in heart or that every MAGE-A3 receptor is unsafe.", "trial_registration_urls": [ "https://clinicaltrials.gov/study/NCT01350401", "https://clinicaltrials.gov/study/NCT01352286" ] }, { "cohort_id": "ima202_16", "product_id": "ima202", "trial_ids": [ "NCT03441100" ], "patients_treated": 16, "population": "MAGE-A1-positive advanced solid tumors", "source": "magea1_2024", "source_sections": "Results: safety and Discussion; primary abstract for Morgan 2013", "review_status": "reviewed", "grade45_specificity": "none_identified", "follow_up": "Published cohort snapshot; later trials are not pooled.", "overlap_note": "One cohort per publication; repeated infusions and mechanistic follow-up do not add patients.", "finding": "Severe cytopenias and one grade 3 CRS occurred. No on-target/off-tumor toxicity was observed; fatal dyspnea was considered unrelated.", "qualification": "The primary paper header lists other MAGEA1 trials; IMA202-101 identity is independently linked by the Columbia trial listing. No objective RECIST responses were required for this safety-only credit.", "trial_registration_urls": [ "https://clinicaltrials.gov/study/NCT03441100" ], "trial_identity_source": "https://recruit.cumc.columbia.edu/studyinfopage/1955" }, { "cohort_id": "adp_a2m10_nsclc_11", "product_id": "adp_a2m10", "trial_ids": [ "NCT02592577" ], "patients_treated": 11, "population": "Advanced non-small cell lung cancer", "source": "magea10_2022", "source_sections": "Results: safety and Discussion; primary abstract for Morgan 2013", "review_status": "reviewed", "grade45_specificity": "none_identified", "follow_up": "Published cohort snapshot; later trials are not pooled.", "overlap_note": "One cohort per publication; repeated infusions and mechanistic follow-up do not add patients.", "finding": "One grade 4 CRS and one treatment-related death after repeat infusion/intensified conditioning. Investigations favored conditioning over MAGE-A10-mediated marrow injury.", "qualification": "Patient marrow antigen testing was limited by specimen quality; absence of engineered-cell enrichment does not prove no risk.", "trial_registration_urls": [ "https://clinicaltrials.gov/study/NCT02592577" ] }, { "cohort_id": "tbi1301_9", "product_id": "tbi1301", "trial_ids": [ "NCT02366546" ], "patients_treated": 9, "population": "NY-ESO-1-positive advanced solid tumors", "source": "tbi1301_2022", "source_sections": "Results: safety and Discussion; primary abstract for Morgan 2013", "review_status": "reviewed", "grade45_specificity": "none_identified", "follow_up": "Published cohort snapshot; later trials are not pooled.", "overlap_note": "One cohort per publication; repeated infusions and mechanistic follow-up do not add patients.", "finding": "One grade 3 lung injury with TCR-T infiltration; resolved with steroids. Authors favored cytokine-mediated capillary leak but could not exclude normal-peptide recognition.", "qualification": "Retain unresolved specificity as a review hold for this product; do not borrow favorable c259 evidence to clear TBI-1301.", "trial_registration_urls": [ "https://clinicaltrials.gov/study/NCT02366546" ] }, { "cohort_id": "magea3_a2_neuro_9", "product_id": "magea3_a2_neuro", "trial_ids": [ "NCT01273181" ], "patients_treated": 9, "population": "Advanced cancers", "source": "magea3_neuro_2013", "source_sections": "Results: safety and Discussion; primary abstract for Morgan 2013", "review_status": "reviewed", "grade45_specificity": "suspected_or_confirmed", "follow_up": "Published cohort snapshot; later trials are not pooled.", "overlap_note": "One cohort per publication; repeated infusions and mechanistic follow-up do not add patients.", "finding": "Three neurological events, including two fatal cases. Authors implicated cross-recognized MAGE-A12 in brain.", "qualification": "Brain staining recognized multiple MAGE-family proteins; MAGE-A12 attribution is supported but not uniquely proven.", "trial_registration_urls": [ "https://clinicaltrials.gov/study/NCT01273181" ] } ], "events": [ { "event_id": "lete_late_cardiac_death", "product_id": "lete_cel_c259", "cohort_id": "lete_mrcls_20", "source": "lete_mrcls_2025", "source_sections": "Safety", "event": "Fatal cardiac arrest, day 161", "patients": 1, "grade": 5, "grade_basis": "Fatal outcome", "treatment_attribution": "potentially_related", "specificity_attribution": "not_established", "mechanism": "unresolved", "affected_tissue": "heart", "recognized_protein": null, "details": "Progressive disease, hypotension, renal insufficiency and intervening radiation/pazopanib complicate attribution. The report does not establish CTAG2-mediated heart injury.", "seriousness_basis": "fatal_outcome" }, { "event_id": "lete_gbs_cases", "product_id": "lete_cel_c259", "cohort_id": null, "source": "lete_gbs_2019", "source_sections": "Case presentations; Discussion", "event": "Guillain-Barre / inflammatory demyelinating neuropathy", "patients": 2, "grade": null, "grade_basis": "GBS severity not assigned a CTCAE grade in the case report; do not infer grade from disability", "treatment_attribution": "suspected", "specificity_attribution": "not_established", "mechanism": "unresolved", "affected_tissue": "peripheral nerves", "recognized_protein": null, "details": "Authors suspected treatment association and discussed indirect immune effects. No identified peptide cross-reaction explains the cases. Case reports have no independent treated-cohort denominator and confer no favorable credit.", "seriousness_basis": "hospitalization_or_major_intervention" }, { "event_id": "ima203_crs_transaminitis", "product_id": "ima203", "cohort_id": "ima203_phase1_40", "source": "ima203_2025", "source_sections": "Safety", "event": "Grade 4 transaminitis during a grade 3 CRS episode", "patients": 1, "grade": 4, "grade_basis": "Reported grade 4 transaminitis; CRS itself graded 3", "treatment_attribution": "related", "specificity_attribution": "not_established", "mechanism": "systemic_inflammation", "affected_tissue": "liver", "recognized_protein": null, "details": "Recorded as part of CRS, without evidence that the TCR recognized PRAME in hepatocytes.", "seriousness_basis": "severe_grade_seriousness_not_separately_reported" }, { "event_id": "afami_aplasia_death", "product_id": "afami_cel_c1032", "cohort_id": "afami_phase1_38", "source": "afami_phase1_2023", "source_sections": "Safety; Discussion", "event": "Fatal aplastic anemia, day 55", "patients": 1, "grade": 5, "grade_basis": "Fatal outcome", "treatment_attribution": "possibly_related", "specificity_attribution": "not_supported", "mechanism": "conditioning_and_inflammation", "affected_tissue": "bone marrow", "recognized_protein": null, "details": "No marrow MAGE-A4 or enrichment of engineered T cells was detected; conditioning and systemic inflammation were considered contributors.", "seriousness_basis": "fatal_outcome" }, { "event_id": "afami_stroke_death", "product_id": "afami_cel_c1032", "cohort_id": "afami_phase1_38", "source": "afami_phase1_2023", "source_sections": "Safety", "event": "Fatal ischemic cerebrovascular accident, day 17", "patients": 1, "grade": 5, "grade_basis": "Fatal outcome", "treatment_attribution": "possibly_related", "specificity_attribution": "not_established", "mechanism": "unresolved", "affected_tissue": "brain", "recognized_protein": null, "details": "Occurred after grade 3 neurotoxicity; no demonstrated MAGE-A4-specific brain injury mechanism was reported.", "seriousness_basis": "fatal_outcome" }, { "event_id": "magea3_titin_deaths", "product_id": "magea3_a3a", "cohort_id": "magea3_a3a_two_cases", "source": "magea3_titin_2013", "source_sections": "Post-clinical investigations; Discussion", "event": "Fatal cardiac injury with titin cross-recognition", "patients": 2, "grade": 5, "grade_basis": "Fatal outcomes", "treatment_attribution": "related", "specificity_attribution": "suspected", "mechanism": "off_target_cross_reactivity", "affected_tissue": "heart", "recognized_protein": "TTN", "details": "Mechanistic work identified titin as the likely unintended target; MAGE antigens were not detected in patient heart samples.", "seriousness_basis": "fatal_outcome" }, { "event_id": "ima202_fatal_dyspnea", "product_id": "ima202", "cohort_id": "ima202_16", "source": "magea1_2024", "source_sections": "Safety; Discussion", "event": "Fatal dyspnea", "patients": 1, "grade": 5, "grade_basis": "Fatal outcome", "treatment_attribution": "unrelated", "specificity_attribution": "not_supported", "mechanism": "unrelated", "affected_tissue": "lung", "recognized_protein": null, "details": "Investigators considered this death unrelated to treatment; severe conditioning cytopenias and grade 3 CRS occurred in the cohort.", "seriousness_basis": "fatal_outcome" }, { "event_id": "magea10_grade4_crs", "product_id": "adp_a2m10", "cohort_id": "adp_a2m10_nsclc_11", "source": "magea10_2022", "source_sections": "Safety; Discussion", "event": "Grade 4 CRS", "patients": 1, "grade": 4, "grade_basis": "Reported CTCAE grade", "treatment_attribution": "related", "specificity_attribution": "not_established", "mechanism": "systemic_inflammation", "affected_tissue": "systemic", "recognized_protein": null, "details": "Required intensive supportive care; symptoms resolved. The subsequent death of this patient was attributed to disease progression.", "seriousness_basis": "reported_serious_event" }, { "event_id": "magea10_aplasia_death", "product_id": "adp_a2m10", "cohort_id": "adp_a2m10_nsclc_11", "source": "magea10_2022", "source_sections": "Safety; Discussion", "event": "Fatal marrow aplasia, sepsis and respiratory distress after repeat infusion", "patients": 1, "grade": 5, "grade_basis": "Fatal outcome", "treatment_attribution": "related", "specificity_attribution": "not_supported", "mechanism": "conditioning_and_infection", "affected_tissue": "bone marrow", "recognized_protein": null, "details": "Authors favored intensified lymphodepletion; patient marrow antigen testing was limited. Fatality was 98 days after the second infusion.", "seriousness_basis": "fatal_outcome" }, { "event_id": "tbi1301_lung_injury", "product_id": "tbi1301", "cohort_id": "tbi1301_9", "source": "tbi1301_2022", "source_sections": "Safety; Discussion", "event": "Steroid-responsive lung injury with TCR-T infiltration", "patients": 1, "grade": 3, "grade_basis": "Reported CTCAE grade", "treatment_attribution": "related", "specificity_attribution": "unresolved", "mechanism": "unresolved", "affected_tissue": "lung", "recognized_protein": null, "details": "Cytokine-mediated capillary leak was favored, but normal-peptide recognition remained a possibility. Below grade 4 does not mean clinically irrelevant.", "seriousness_basis": "hospitalization_or_major_intervention" }, { "event_id": "magea3_neurological_deaths", "product_id": "magea3_a2_neuro", "cohort_id": "magea3_a2_neuro_9", "source": "magea3_neuro_2013", "source_sections": "Safety; Discussion", "event": "Fatal neurological injury; MAGE-A12 cross-recognition implicated", "patients": 2, "grade": 5, "grade_basis": "Fatal outcome", "treatment_attribution": "related", "specificity_attribution": "suspected", "mechanism": "cross_recognized_family_peptide", "affected_tissue": "brain", "recognized_protein": "MAGEA12", "details": "Two deaths among three neurological cases in nine treated patients; the third recovered. Attribution of normal brain antigen to MAGE-A12 is proposed rather than exclusive.", "seriousness_basis": "fatal_outcome" } ], "sequence_audit": { "source_url": "https://ftp.ensembl.org/pub/release-115/fasta/homo_sapiens/pep/Homo_sapiens.GRCh38.pep.all.fa.gz", "sha256": "7991ab37d09986eefdb5c77032b15370ab0e99918b78f235f3230c0302851c96", "scope": "Verified listed peptide-to-locus/isoform links; not an exhaustive proteome-wide epitope search." } }