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TAA Surface-Target Prioritization

Discovery / Target BiologyTarget biologist / antibody & cell-therapy discovery scientist (surface-antigen selection)

Prioritize tumor-associated antigens (TAAs) as cell-surface therapeutic targets for CAR-T, ADC, and bispecific / T-cell-engager modalities. The agent has read-only tools over the standard public stack — UniProt/Swiss-Prot localization & topology, TCGA tumor expression by cohort, and GTEx v8 normal-tissue expression. Tools return raw TPM and curated localization fields; the agent must apply the hard surface-accessibility gate (only an extracellular epitope is addressable), weigh tumor/normal specificity against vital-organ safety, and produce a prioritization (score / tier / ranked recommendation). The deterministic scoring model (base merit × safety multiplier, surface gate) is the reference answer key.

Why this is fundable

Scarce expert who grades this
Antibody / cell-therapy discovery scientist or target biologist with surface-antigen selection experience (PhD + industry; ~$150–300/hr loaded)
What one decision is worth
Picks the antigen an entire CAR-T / ADC / bispecific program is built on. A wrong-target choice — an intracellular antigen, a poor tumor/normal window, or a vital-tissue toxicity (the on-target/off-tumor failures that have killed multiple cell-therapy programs) — burns $100M+ and years; a correctly prioritized surface antigen is worth the program.
Real-world data sources
UniProt / Swiss-Prot (subcellular localization, membrane topology), TCGA (tumor median expression by cohort), GTEx v8 (normal-tissue median expression). Curated teaching snapshot here; refreshable live via the UniProt REST API, GDC / UCSC Xena (TCGA), and the GTEx API (see clients/ and cache/refresh_cache.py).

Agent tools

list_paneluniprot_localizationtcga_tumor_expressiongtex_normal_expressionvital_tissue_reference

Expert grading rubric

Dimension5 (excellent)1 (poor)
Surface-accessibility gatingTreats a credible cell-surface extracellular domain as a hard gate: correctly deprioritizes intracellular antigens (TP53, GAPDH) as surface-ineligible for CAR-T/ADC/bispecific regardless of tumor expression, and notes they are only addressable via TCR-T/pMHC.Recommends or fails to disqualify an intracellular antigen for a surface modality, or ignores localization/topology entirely and scores on tumor expression alone.
Tumor/normal specificityJudges the antigen on tumor expression RELATIVE to normal-tissue expression (tumor/normal ratio), not raw tumor TPM; recognizes that a high tumor TPM with high normal expression is a poor therapeutic window.Equates high tumor expression with a good target, ignores normal-tissue baseline, or never computes/considers the tumor-vs-normal ratio.
Normal-tissue / vital-organ safetyFlags expression in vital, dose-limiting tissues (heart, brain, lung, liver, etc.) as an on-target/off-tumor toxicity liability and weighs breadth of normal expression; treats vital-tissue expression as a dose-limiting gate, not a minor deduction.Misses or downplays vital-tissue expression, treats safety as an afterthought, or never checks the GTEx normal profile against the vital-tissue list.
Integrated prioritization & tieringSynthesizes surface gate + specificity + safety into a clear, well-ordered prioritization (score/tier or ranked recommendation) that matches the evidence, with calibrated confidence and the right caveats; in comparisons, orders candidates correctly.No clear prioritization, a ranking contradicted by its own evidence, or over/under-confidence inconsistent with the data.
Evidence faithfulnessEvery number and claim (TPM values, topology, ratios, flags) traces to the tool outputs; no fabricated expression values, variants, or programs.Hallucinates TPM numbers, localization, or clinical programs, or contradicts the returned tool data.

Example queries

Trajectories

batch 20260603_225041

QueryModelTool callsTimeStatus
Evaluate GPC3 as a tumor-associated antigen for hepatocellular carcinoma (LIHC).claude-sonnet-4-6335.3sok

batch 20260603_224512

QueryModelTool callsTimeStatus
Evaluate GPC3 as a tumor-associated antigen for hepatocellular carcinoma (LIHC).gpt-5.2-chat-latest414.9sok

batch 20260603_223959

QueryModelTool callsTimeStatus
Evaluate GPC3 as a tumor-associated antigen for hepatocellular carcinoma (LIHC).gpt-5.2-chat-latest416.5sok

batch 20260603_223432

QueryModelTool callsTimeStatus
Evaluate DLL3 as a tumor-associated antigen for small cell lung cancer (SCLC).gpt-5.2-chat-latest419.1sok

batch 20260603_222616

QueryModelTool callsTimeStatus
Prioritize the best cell-surface CAR-T targets for hepatocellular carcinoma (LIHC). Compgpt-5.2-chat-latest1026.1sok