D-WS5-001
SCF Ranked Antigen Candidate Library (RACL)
PROJECT HELIX-HTT | Huntington’s-Adjacent Neuro-Oncology Vaccine Program
DOCUMENT CONTROL HEADER
Program Code: SCF-ARGEN-HTT-NO-01
Workflow Stage: Discovery Phase
Deliverable: Core Deliverable #7
Document Code: SCF-RACL-NO-0001
Purpose: Generate the final ranked inventory of vaccine candidate antigens by integrating genomic, transcriptomic, HLA, immunopeptidomic, microenvironment, safety, and SCF-specific biological intelligence layers.
1. PURPOSE OF THE RANKED ANTIGEN CANDIDATE LIBRARY
The Ranked Antigen Candidate Library (RACL) represents the first true decision-making layer of the Discovery Program.
Previous deliverables identified:
- Mutations
- Expression
- HLA compatibility
- Presented antigens
- Tumor terrain
The RACL answers:
Which antigens should actually be included in the vaccine?
2. INTEGRATION ARCHITECTURE
Mutation Catalog
+
Expression Atlas
+
HLA Compatibility Matrix
+
Presented Antigen Library
+
SCF-MES Report
↓
Antigen Ranking Engine
↓
Ranked Antigen Candidate Library3. RACL ANTIGEN CLASSES
CLASS A
Personalized Neoantigens
Priority:
Highest
Requirements:
✓ Somatic mutation
✓ Expression confirmed
✓ HLA compatible
✓ Presented by immunopeptidomics
✓ Low CNS risk
CLASS B
Fusion Neoantigens
Priority:
Highest
Requirements:
✓ Fusion-specific junction
✓ Strong presentation
✓ Tumor restricted
CLASS C
Tumor-Associated Antigens
Priority:
Moderate–High
Requirements:
✓ Tumor enriched
✓ Low normal CNS expression
CLASS D
Alternative Splice Antigens
Priority:
Moderate–High
Requirements:
✓ Tumor-specific splice event
✓ Presentation confirmed
CLASS E
SCF Experimental Stress Antigens
Priority:
Research Program
Requirements:
✓ DNA repair stress signature
✓ Hypoxia adaptation
✓ Neuroimmune remodeling
4. MASTER ANTIGEN RANKING TABLE
RACL TABLE 1
Rank | Antigen ID | Class | APS | MES | Safety | Decision |
1 | Example | Neoantigen | 95 | 88 | Green | Include |
2 | Example | Fusion | 93 | 84 | Green | Include |
3 | Example | Neoantigen | 89 | 82 | Green | Include |
4 | Example | TAA | 78 | 80 | Yellow | Backup |
5 | Example | Stress Antigen | 71 | 76 | Yellow | Exploratory |
5. ANTIGEN PRIORITY SCORE (APS)
Purpose
Provide unified ranking.
APS Formula
APS =
Tumor Specificity
+
Expression Strength
+
HLA Presentation
+
Immunopeptidomics Confirmation
+
Clonality
+
Microenvironment Compatibility
-
CNS Risk
-
Immune Escape Risk6. SCF ANTIGEN EVIDENCE HIERARCHY
Tier I
Highest Confidence
Requirements:
✓ Genomics
✓ RNA Expression
✓ HLA Binding
✓ Immunopeptidomics
✓ Favorable MES
Tier II
High Confidence
Requirements:
✓ Genomics
✓ Expression
✓ HLA
No immunopeptidomic confirmation
Tier III
Exploratory
Requirements:
✓ Genomic evidence
Limited validation
7. IMMUNE ACTIVATION POTENTIAL
Composite Immune Activation Index (CIAI)
Measures:
- CD8 activation probability
- CD4 activation probability
- Immune memory potential
Classification
CIAI | Interpretation |
>85 | Strong |
70–85 | Moderate |
50–69 | Limited |
<50 | Weak |
8. IMMUNE ESCAPE RISK ASSESSMENT
Purpose
Identify antigens likely to be lost during tumor evolution.
Factors
Factor | Risk |
Subclonal mutation | Elevated |
Expression instability | Elevated |
HLA loss | Elevated |
Antigen processing defects | Elevated |
Risk Classes
Class | Interpretation |
ER-A | Low Risk |
ER-B | Moderate Risk |
ER-C | High Risk |
9. CNS SAFETY MATRIX
Objective
Prevent vaccine-induced neurotoxicity.
Safety Domains
Domain | Assessment |
Neuronal homology | Similarity analysis |
Brain expression | Tissue atlas review |
Autoimmune risk | Predicted CNS targeting |
Neuroinflammation | Neuroimmune compatibility |
Safety Classification
Class | Meaning |
Green | Include |
Yellow | Review |
Red | Exclude |
10. SCF MICROENVIRONMENT INTEGRATION
Antigens receive adjustment based upon:
SCF-MES
Components:
- Immune accessibility
- Presentation competence
- Redox burden
- Hypoxia burden
- Neuroimmune compatibility
MES Adjustment
MES Class | Effect |
MES-A | Promote |
MES-B | Neutral |
MES-C | Downgrade |
MES-D | Exclude |
11. FINAL DECISION CLASSES
CLASS A
Primary Vaccine Candidate
Requirements:
APS ≥ 85
CLASS B
Backup Vaccine Candidate
Requirements:
APS 70–84
CLASS C
Exploratory Candidate
Requirements:
APS 55–69
CLASS X
Excluded
Requirements:
APS < 55 or safety failure
12. VACCINE ASSEMBLY RECOMMENDATIONS
Primary Set
8–20 antigens
Composition:
- 60–70% Neoantigens
- 10–20% Fusion antigens
- 10–20% Tumor-associated antigens
Backup Set
3–5 antigens
Used for:
- Escape prevention
- Manufacturing redundancy
Experimental Set
1–3 SCF Stress Antigens
Research deployment only
13. RACL OUTPUT FILES
RACL-01
Complete Ranked Antigen Library
RACL-02
Class A Vaccine Candidate List
RACL-03
Backup Antigen List
RACL-04
Experimental Antigen List
RACL-05
Immune Escape Risk Report
RACL-06
CNS Safety Report
14. DECISION GATE
Advance to Vaccine Candidate Package generation if:
✓ Antigen ranking complete
✓ APS assigned
✓ MES integration complete
✓ Safety review complete
✓ Candidate sets selected
DELIVERABLE SUMMARY
The Ranked Antigen Candidate Library provides:
- Final antigen prioritization
- Vaccine assembly guidance
- Safety governance
- Immune escape analysis
- SCF microenvironment integration
It represents the final selection layer before vaccine construct design.
STATUS
Core Deliverable #7: COMPLETE
NEXT DELIVERABLE: Core Deliverable #8 — SCF Vaccine Candidate Package (VCP)
This final deliverable will integrate all previous outputs into a complete IND-facing vaccine development package, including construct architecture, antigen composition strategy, adjuvant strategy, companion diagnostics, preclinical development roadmap, and Go/No-Go development criteria.