{ "figure_id": "P01", "research_parent_version": "ADC-20261007-R1", "evidence_as_of": "2026-10-07", "timezone": "Asia/Taipei", "parent_figure_ids": [ "F03", "F04" ], "parent_master_sha256": "ba5a46bc85a086921ef421928922e515d24c3a51283bd5c4c9dd5e9f0f077f0c", "data_type": "qualitative mechanism model; no measured numerical values", "nodes": [ { "id": "adc", "compartment": "extracellular", "label_zh": "完整 ADC", "label_en": "Intact ADC", "source_ids": [ "R02" ] }, { "id": "premature_payload", "compartment": "extracellular", "label_zh": "若過早釋放的游離負載", "label_en": "Conditionally premature free payload", "source_ids": [ "R02", "R06" ] }, { "id": "antigen", "compartment": "plasma_membrane", "label_zh": "膜上靶點", "label_en": "Surface antigen", "source_ids": [ "R02" ] }, { "id": "bound_adc", "compartment": "extracellular_membrane_invagination", "label_zh": "結合靶點的 ADC", "label_en": "Antigen-bound ADC", "source_ids": [ "R02" ] }, { "id": "endosome", "compartment": "intracellular_vesicle_lumen", "label_zh": "胞內體中的 ADC", "label_en": "ADC in endosomal lumen", "source_ids": [ "R02", "R10" ] }, { "id": "lysosome", "compartment": "intracellular_vesicle_lumen", "label_zh": "溶小體", "label_en": "Lysosome", "source_ids": [ "R02", "R06" ] }, { "id": "active_payload", "compartment": "cytoplasm", "label_zh": "活性負載", "label_en": "Active payload", "source_ids": [ "R02", "R06" ] }, { "id": "topoi_action", "compartment": "nucleus", "label_zh": "Topo-I 抑制；DNA 損傷", "label_en": "Topo-I inhibition; DNA damage", "source_ids": [ "R03" ] }, { "id": "microtubule_action", "compartment": "cytoplasm", "label_zh": "微管抑制；阻礙細胞分裂", "label_en": "Microtubule inhibition; blocked cell division", "source_ids": [ "R06" ] } ], "edges": [ { "from_node": "adc", "to_node": "bound_adc", "meaning_zh": "Fab結合抗原胞外端", "meaning_en": "Fab binding to the extracellular antigen domain", "visual": "solid_teal", "source_ids": [ "R02" ] }, { "from_node": "adc", "to_node": "premature_payload", "meaning_zh": "若在到達細胞前過早釋放；不是預設路徑", "meaning_en": "Conditional premature release before reaching the cell; not the default route", "visual": "dashed_orange", "source_ids": [ "R02", "R06" ] }, { "from_node": "bound_adc", "to_node": "endosome", "meaning_zh": "內吞；ADC留在囊泡腔內", "meaning_en": "Internalization; ADC remains within the vesicle lumen", "visual": "solid_teal", "source_ids": [ "R02" ] }, { "from_node": "endosome", "to_node": "lysosome", "meaning_zh": "胞內囊泡運輸", "meaning_en": "Intracellular vesicular trafficking", "visual": "solid_teal", "source_ids": [ "R02", "R06", "R10" ] }, { "from_node": "lysosome", "to_node": "active_payload", "meaning_zh": "依設計切斷連接子或分解抗體，活性負載跨出溶小體膜", "meaning_en": "Design-dependent linker cleavage or antibody breakdown; active payload exits across the lysosomal membrane", "visual": "solid_orange", "source_ids": [ "R02", "R06" ] }, { "from_node": "active_payload", "to_node": "topoi_action", "meaning_zh": "替代分支A：活性負載進入細胞核", "meaning_en": "Alternative A: active payload enters the nucleus", "visual": "solid_orange", "source_ids": [ "R03" ] }, { "from_node": "active_payload", "to_node": "microtubule_action", "meaning_zh": "替代分支B：活性負載作用於胞質微管", "meaning_en": "Alternative B: active payload acts on cytoplasmic microtubules", "visual": "solid_orange", "source_ids": [ "R06" ] } ], "failure_points": [ { "id": "F1", "zh": "血中穩定／提前釋放", "en": "Blood stability / premature release", "position": "extracellular ADC before antigen binding", "source_ids": [ "R02", "R06" ], "design_connection": "Linker/coupling design and exposure; not a claim that every early release event has the same toxicity." }, { "id": "F2", "zh": "抗原異質性", "en": "Antigen heterogeneity", "position": "cell surface; if illustrated with density, show distinct cells or clearly label variation across tumour cells", "source_ids": [ "R04", "R06" ], "design_connection": "Target/antibody choices must address actual antigen distribution." }, { "id": "F3", "zh": "胞內遞送", "en": "Intracellular delivery", "position": "endosome-to-lysosome path; no recycling fork", "source_ids": [ "R10" ], "design_connection": "Preclinical anti-HER2 antibody variants with reduced antigen affinity at acidic endosomal pH showed increased lysosomal accumulation of their MMAE ADCs. This modifies antigen binding, not acid-sensitive linker cleavage, and does not validate LYSward." }, { "id": "F4", "zh": "負載抗藥", "en": "Payload resistance", "position": "action branches after active payload release", "source_ids": [ "R03", "R06" ], "design_connection": "Target alteration and efflux can differ by payload; no universal resistance prevalence drawn." } ], "quantitative_units": null, "currency": null, "formula": null, "not_to_scale": [ "cell and organelle size", "molecule count", "antigen density", "arrow width", "distance" ], "exclusions": [ "No bystander pathway is depicted.", "The two payload branches are alternatives, not a dual-payload product.", "No product-specific human benefit is asserted.", "R2 does not depict the previously unverified gray endosomal recycling branch." ], "source_index": "../sources.csv", "generation": "Derived from the original editable P01 vector drawing; only the recycling branch, F3 text, descriptive metadata, source footer and version footer were changed. Each full SVG was rendered with Inkscape to a full PNG.", "parent_pilot_version": "ADC-20261007-R1-VISUAL-PILOT2-1.0", "artifact_version": "ADC-20261007-R1-LAYERED-HTML-R2-1.0", "additional_source_access_date": "2026-10-07", "correction": { "issue": "P01 prior recycling branch and pH design mapping relied only on T14, not directly reverified.", "resolution": "Removed recycled_complex and dashed gray recycling edge; F3 now describes intracellular delivery with direct preclinical support from R10.", "source_replacement": { "removed_from_P01": "T14", "added_to_P01": "R10" }, "other_paths": "unchanged", "numeric_values_added": 0 } }