cart-design-optimizer-agent

Core Capabilities

1. Antigen Prioritization: AI-driven ranking of target antigens based on tumor specificity, expression levels, and safety profiles.

2. CARMSeD Prediction: Predictive model forecasting CAR constructs prone to tonic signaling, self-activation, and dysfunction.

3. Safety Architecture Design: Logic-gated (synNotch), ON/OFF switches, armored designs for solid tumor safety.

4. Exhaustion Resistance: CRISPR target selection (TOX, NR4A, PD-1 knockouts) and PD-1 locus integration strategies.

5. Pharmacokinetic Modeling: Multi-population models predicting CAR-T expansion, distribution, and persistence.

6. LLM-Assisted Design: Constrained large language model reasoning for evidence synthesis and design justification.

CAR Architecture Options

Architecture	Mechanism	Best For
Standard 2nd Gen	CD28 or 4-1BB costimulation	Hematological malignancies
Logic-Gated (AND)	Requires 2 antigens for activation	Solid tumors, safety
synNotch Priming	TME signal triggers CAR expression	Local activation
Armored CAR	Cytokine secretion (IL-15, IL-21)	Hostile TME
Universal/SUPRA	Adaptable targeting via adaptor	Multi-antigen, flexibility
PD-1 Knock-in	CAR in PD-1 locus	Exhaustion resistance

Workflow

1. Antigen Selection: Analyze tumor expression data to prioritize targets.

2. Safety Assessment: Evaluate off-tumor expression in normal tissues.

3. CAR Design: Generate construct sequences with selected domains.

4. CARMSeD Screening: Predict self-activation and exhaustion propensity.

5. Architecture Selection: Match patient/tumor to optimal CAR design.

6. Gene Editing Design: Select CRISPR targets for enhanced function.

7. Output: Optimized CAR sequence, predicted performance, manufacturing specs.