--- name: 'nk-cell-therapy-agent' description: 'AI-powered NK cell therapy design for cancer immunotherapy including CAR-NK engineering, memory-like NK generation, and KIR/HLA matching optimization.' measurable_outcome: Execute skill workflow successfully with valid output within 15 minutes. allowed-tools: - read_file - run_shell_command --- # NK Cell Therapy Agent The **NK Cell Therapy Agent** provides AI-driven design and optimization of natural killer cell therapies for cancer treatment. It covers CAR-NK engineering, cytokine-induced memory-like (CIML) NK generation, KIR/HLA matching, and NK cell expansion optimization. ## When to Use This Skill * When designing CAR-NK constructs for tumor targeting. * To optimize KIR/HLA mismatch for allogeneic NK therapy. * For generating memory-like NK cells with enhanced persistence. * When predicting NK cell activation against specific tumor types. * To analyze NK cell receptor repertoires and function. ## Core Capabilities 1. **CAR-NK Design**: Design chimeric antigen receptors optimized for NK cell biology (NK-specific signaling domains). 2. **KIR/HLA Matching**: Predict KIR-HLA interactions for donor selection in allogeneic therapy. 3. **Memory-Like NK Generation**: Optimize CIML protocol with IL-12/15/18 cytokine preactivation. 4. **Expansion Optimization**: ML models for feeder-free NK expansion conditions. 5. **Tumor Target Prediction**: Match NK receptor profiles to tumor ligand expression. 6. **Persistence Enhancement**: Engineering strategies for improved in vivo survival. ## NK Cell Advantages Over T Cells | Feature | NK Cells | T Cells | |---------|----------|---------| | MHC requirement | No | Yes | | Allogeneic use | Yes (no GVHD) | Limited (GVHD risk) | | CRS risk | Lower | Higher | | Off-the-shelf | Yes | Autologous typical | | Antigen escape | Multiple receptors | Single CAR | | Persistence | Shorter | Longer | ## CAR-NK Architecture ``` [scFv] - [Hinge] - [Transmembrane] - [Costimulatory] - [Signaling] NK-Optimized Domains: - Transmembrane: NKG2D, CD8α, or CD28 - Costimulatory: 2B4, DAP10, or CD28 - Signaling: CD3ζ (with NK-specific adaptations) - Additional: Cytokine secretion (IL-15), suicide switch ``` ## Workflow 1. **Input**: Target antigen, tumor type, NK source (PB, UCB, iPSC, cell line). 2. **CAR Design**: Generate optimized CAR-NK construct sequence. 3. **KIR Analysis**: Determine KIR genotype and HLA matching for donors. 4. **Activation Protocol**: Optimize cytokine cocktail for desired phenotype. 5. **Expansion**: Design feeder-based or feeder-free expansion protocol. 6. **Quality Prediction**: Predict NK product functionality. 7. **Output**: CAR sequence, donor recommendations, expansion protocol, QC metrics. ## Example Usage **User**: "Design a CAR-NK targeting CD19 for B-cell malignancies with enhanced persistence." **Agent Action**: ```bash python3 Skills/Immunology_Vaccines/NK_Cell_Therapy_Agent/nk_designer.py \ --target CD19 \ --tumor_type b_cell_lymphoma \ --nk_source ucb \ --persistence_strategy il15_secretion \ --costimulatory 2B4_DAP10 \ --donors donor_hla_kir.json \ --output carnk_design/ ``` ## NK Receptor-Ligand Interactions **Activating Receptors**: | Receptor | Ligands | Tumor Expression | |----------|---------|------------------| | NKG2D | MICA/B, ULBPs | Stress-induced | | DNAM-1 | CD155, CD112 | Broadly expressed | | NKp30 | B7-H6, BAG6 | Tumor-specific | | NKp46 | Unknown tumor | Variable | | CD16 | IgG Fc | ADCC trigger | **Inhibitory Receptors**: | Receptor | Ligands | Function | |----------|---------|----------| | KIR2DL1 | HLA-C2 | Self tolerance | | KIR2DL2/3 | HLA-C1 | Self tolerance | | KIR3DL1 | HLA-Bw4 | Self tolerance | | NKG2A | HLA-E | Checkpoint | ## Memory-Like NK (CIML) Protocol **Cytokine Preactivation**: - IL-12 (10 ng/mL) + IL-15 (50 ng/mL) + IL-18 (50 ng/mL) - 16-18 hour stimulation - Enhanced IFN-γ, cytotoxicity upon restimulation - Improved in vivo persistence **Clinical Evidence**: Effective in relapsed/refractory AML ## KIR/HLA Matching Optimization **Missing-Self Recognition**: - Donor KIR + / Patient HLA - - Enhanced NK cytotoxicity - Important for allo-HSCT **Prediction Model**: - Input: Donor KIR genotype, patient HLA - Output: Predicted NK alloreactivity score - Validated in transplant outcomes ## AI/ML Components **CAR-NK Optimization**: - Adapted CARMSeD for NK biology - NK-specific signaling domain preferences - Tonic signaling prediction **Expansion Prediction**: - Fold-expansion from culture conditions - Phenotype shift modeling - Exhaustion marker prediction ## Prerequisites * Python 3.10+ * HLA/KIR databases * NK receptor databases * Flow cytometry analysis tools ## Related Skills * CART_Design_Optimizer_Agent - For CAR engineering principles * Epitope_Prediction_Agent - For target selection * Flow_Cytometry_AI - For NK phenotyping ## Clinical Development **Current CAR-NK Programs**: - CD19 CAR-NK (MD Anderson - AML, lymphoma) - NKG2D CAR-NK (various solid tumors) - CD70 CAR-NK (renal cell carcinoma) - HER2 CAR-NK (breast cancer) ## Author AI Group - Biomedical AI Platform --- Source attribution: FreedomIntelligence Original project: https://github.com/FreedomIntelligence/OpenClaw-Medical-Skills License: MIT License information: https://opensource.org/license/mit Original upstream instructions; downloaded from Dave AI. ## Upstream license notice MIT License Copyright (c) 2026 FridrichMethod Permission is hereby granted, free of charge, to any person obtaining a copy of this software and associated documentation files (the "Software"), to deal in the Software without restriction, including without limitation the rights to use, copy, modify, merge, publish, distribute, sublicense, and/or sell copies of the Software, and to permit persons to whom the Software is furnished to do so, subject to the following conditions: The above copyright notice and this permission notice shall be included in all copies or substantial portions of the Software. THE SOFTWARE IS PROVIDED "AS IS", WITHOUT WARRANTY OF ANY KIND, EXPRESS OR IMPLIED, INCLUDING BUT NOT LIMITED TO THE WARRANTIES OF MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE AND NONINFRINGEMENT. IN NO EVENT SHALL THE AUTHORS OR COPYRIGHT HOLDERS BE LIABLE FOR ANY CLAIM, DAMAGES OR OTHER LIABILITY, WHETHER IN AN ACTION OF CONTRACT, TORT OR OTHERWISE, ARISING FROM, OUT OF OR IN CONNECTION WITH THE SOFTWARE OR THE USE OR OTHER DEALINGS IN THE SOFTWARE. --- NOTE ON BUNDLED CONTENT This repository aggregates skills from multiple upstream projects (see the README for the source list). Each `skills//` directory may carry its own license inherited from its upstream source. The MIT license above applies to this repository's curation and the scripts/workflows in `/`, `/scripts/`, and `/.github/` — not to the upstream skill content itself. Consult the upstream repository linked in the README and any LICENSE file inside a skill directory before reusing skill content commercially. # Dave AI resource metadata Creator / publisher: FreedomIntelligence Original project: https://github.com/FreedomIntelligence/OpenClaw-Medical-Skills Attribution basis: Exact package in biomedical source index and publisher source table Fields of work: Healthcare & Life Sciences Roles: Clinical Research, Health Informatics, Medical Writer Specialties: API Tools: Python Country applicability: Country not specified Classification basis: Source catalog labels Instruction SHA-256: e88db0576dba9975d2f1006851417c29d4d56767526d13ef59984fa5b497217c Metadata reviewed: 2026-10-27 This metadata supersedes earlier Dave AI catalog attribution. Original instruction and supporting files are preserved.