Patient Co-Owned mRNA Neoantigen Anti-Cancer Vaccines Protected by Biosample NFTs

A Framework for Democratizing Personalized Cancer Immunotherapy Through Blockchain-Verified Patient Sovereignty

1. Introduction: The Patient Ownership Problem

1.1 The Current Paradigm

In 2023, BioNTech and Genentech published landmark Phase 1 results demonstrating that individualized mRNA neoantigen vaccines could induce durable T-cell responses in patients with resected pancreatic ductal adenocarcinoma (PDAC)—one of the deadliest cancers with an 88% mortality rate.¹ The vaccine, autogene cevumeran, showed remarkable efficacy: eight of sixteen patients developed vaccine-induced immune responses, with six of those eight remaining cancer-free at three-year follow-up.²

This represents a genuine breakthrough. However, the trial also illuminates a fundamental asymmetry in the patient-pharma relationship:

The patient is transformed from a human being with cancer into raw material in a value chain where they have zero ownership stake. Their unique genetic signature—the very mutations that make their cancer both deadly and potentially targetable—becomes the intellectual property of corporations.

1.2 The Scale of the Problem

The global market for mRNA cancer vaccines is projected to exceed $5-7 billion by 2030, with compound annual growth rates surpassing 30%.³ First regulatory approvals are anticipated by 2027-2029. Yet patients—the source of every neoantigen, every tissue sample, every immune response that validates these therapies—are positioned to share in none of this value.

1.3 The Alternative: Patient Co-Ownership

This whitepaper proposes a fundamentally different model: one where patients retain ownership of their neoantigen sequences and chain of custody through manufacturing, enabled by blockchain-verified Biosample NFTs (BioNFTs). This model does not require pharmaceutical companies to change their practices—it creates a parallel pathway for patients who choose to exercise sovereignty over their own biology.

"The question is not whether personalized cancer vaccines work—the science increasingly suggests they do. The question is: who owns the vaccine derived from your own tumor?"

2. The Science of Personalized mRNA Neoantigen Vaccines

2.1 Mechanism of Action

Personalized mRNA neoantigen vaccines work by teaching the patient's immune system to recognize and attack cancer cells expressing tumor-specific mutations. The process involves several key steps:

2.1.1 Neoantigen Identification

Neoantigens are peptide sequences derived from somatic mutations in tumor cells that are presented on the cell surface by major histocompatibility complex (MHC) molecules. Unlike tumor-associated antigens, which are also expressed on normal cells, neoantigens are truly tumor-specific and therefore represent ideal targets for immunotherapy.⁴

The identification process requires:

• Whole-exome sequencing (WES) of tumor and matched normal tissue to identify somatic mutations
• RNA sequencing (ESSENTIAL) to confirm expression of mutated genes—a mutation that is not expressed cannot generate a targetable neoantigen
• HLA typing to determine which mutant peptides can be presented by the patient's MHC molecules
• Computational prediction of peptide-MHC binding affinity using validated tools (see below)
• Prioritization algorithms incorporating clonality, expression level, and immunogenicity predictions

2.1.2 Neoantigen Prediction Tools

Multiple computational tools are available for neoantigen identification and prioritization:

These tools are publicly available and can be deployed by qualified bioinformatics teams, enabling patient-directed neoantigen discovery independent of pharmaceutical company pipelines.

2.1.3 mRNA Vaccine Design

Once neoantigens are identified, mRNA sequences encoding these peptides are designed and synthesized. Key technical considerations include:

2.1.4 Immune Activation

Upon injection, mRNA is taken up by antigen-presenting cells, translated into neoantigen peptides, and presented on MHC molecules. This triggers both CD8+ cytotoxic T-cell responses (which directly kill tumor cells) and CD4+ helper T-cell responses (which coordinate the immune attack).

2.2 Clinical Evidence: The BioNTech/Genentech PDAC Trial

The most compelling evidence for personalized mRNA neoantigen vaccines comes from the Phase 1 trial of autogene cevumeran in resected pancreatic cancer:^1,2

Critically, 98% of the T cells targeting individual neoantigens were de novo—meaning they were not detectable before vaccination. The vaccine created entirely new immune responses against the patient's specific tumor mutations.

2.3 KRAS-Targeted Vaccines: A Complementary Approach

While fully personalized vaccines target patient-specific neoantigens, "off-the-shelf" vaccines targeting common oncogenic mutations represent a parallel development track. KRAS mutations, present in >90% of pancreatic cancers, are particularly attractive targets:

The patient case study presented below represents an ideal candidate for both approaches: personalized neoantigen vaccination and KRAS G12D-targeted therapy.

3. Clinical Case Study: Resectable PDAC with KRAS G12D

3.1 Clinical Presentation

3.2 Pathologic Diagnosis

Fine-needle biopsy of the pancreatic head lesion confirmed adenocarcinoma. The specimen was reviewed at intradepartmental conference with concurrence on the diagnosis.

3.3 Comprehensive Genomic Profiling

3.3.1 Somatic Tumor Mutations (Caris Life Sciences MI Profile)

3.3.2 Genomic Signatures

3.3.3 HLA Genotype (Predicted from Tumor Sequencing)

3.3.4 Germline Testing (Invitae 62-Gene Panel)

Result: NEGATIVE

No pathogenic or likely pathogenic germline variants were identified in 62 genes associated with hereditary cancer syndromes, including BRCA1, BRCA2, PALB2, ATM, and MLH1/MSH2/MSH6/PMS2.

This confirms the somatic (tumor-only) origin of the KRAS and TP53 mutations—they arose in the tumor and are not inherited.

3.4 Staging Imaging

3.4.1 PET/CT Findings (January 2026)

3.5 Neoantigen Vaccine Candidacy Assessment

Based on the comprehensive molecular and clinical profile, this patient demonstrates multiple features that make them an ideal candidate for personalized neoantigen vaccination:

3.6 The Whipple Specimen: The Essential Source Material

This is why tissue handling at the time of surgery is critical. The tumor specimen must be:

1. Immediately preserved in RNA-stabilizing solution (RNAlater) or snap-frozen in liquid nitrogen
2. Processed within hours to prevent RNA degradation
3. Stored at -80°C for long-term preservation
4. Protected by the patient's BioNFT establishing chain of custody and ownership

The Whipple surgical specimen is not just tissue—it is the irreplaceable biological source code for the patient's personalized cancer vaccine.

3.7 Treatment Window

Following surgical resection (Whipple procedure), there is typically a 6-12 week recovery period before adjuvant chemotherapy begins. This window represents the critical opportunity for personalized vaccine manufacturing and initial dosing—the same approach used in the BioNTech trial.

4. BioNFT Architecture: Technical Framework for Patient Sovereignty

4.1 The Ownership Problem in Biospecimen Research

Under current practices, patients are disconnected from their donated biospecimen with little to no visibility into how their contributions are being used. Once tissue leaves the patient's body, it enters a chain of custody controlled entirely by healthcare institutions and their commercial partners. The patient loses all rights to:

• Know how their tissue is being used
• Control who has access to their genomic data
• Revoke consent if their preferences change
• Share in economic value derived from their biology

4.2 BioNFT: A Technical Solution

BioNFTs (Biosample Non-Fungible Tokens) are blockchain-based digital tokens that establish verifiable, patient-controlled chain of custody for biospecimens and derived data. The technology is protected by two granted U.S. patents:^5,6

4.2.1 Core Architecture

The BioNFT architecture integrates with Story Protocol for IP management and uses BioFS (GenoBank's GDPR-compliant file system built on AWS S3) for secure, deletable storage. Unlike IPFS, BioFS supports the "right to erasure" required by GDPR Article 17.

4.2.2 Key Technical Components

4.2.3 Metamorphic Consent

Unlike traditional informed consent (a static document signed once), BioNFT enables "Metamorphic Consent"—consent that transforms from a static permission into an ongoing economic relationship. Key features:

• Revocability: Patient can revoke consent at any time; smart contract immediately restricts access
• Granularity: Different consent levels for different uses (research vs. commercial vs. AI training)
• Transparency: Patient sees exactly who accesses their data and when
• Economic Participation: Smart contracts can encode revenue-sharing terms

4.3 Application to Personalized Vaccine Manufacturing

In the context of patient co-owned mRNA neoantigen vaccines, BioNFTs serve as the legal and technical infrastructure for maintaining patient sovereignty throughout the manufacturing process:

4.4 Legal Framework

The BioNFT approach operates within existing legal frameworks while establishing clearer patient rights:

• HIPAA Compliance: Protected health information is encrypted and access-controlled; patient controls disclosure
• GDPR Article 17: Right to erasure is enforceable through revocable consent (critical reason for AWS S3 vs. IPFS)
• Common Rule (45 CFR 46): Informed consent is documented on blockchain with clear terms
• IP Ownership: Smart contract explicitly assigns neoantigen sequence IP to patient; CDMO provides manufacturing service only

5. Manufacturing Partnership Model

5.1 CDMO Landscape for Personalized mRNA

Several contract development and manufacturing organizations (CDMOs) have established capabilities for GMP-grade mRNA synthesis. Leading candidates for patient co-owned vaccine manufacturing include:

5.2 TriLink BioTechnologies: A Detailed Assessment

TriLink BioTechnologies, part of Maravai LifeSciences (NASDAQ: MRVI), has emerged as a leading CDMO for mRNA therapeutics. Key capabilities relevant to patient co-owned vaccines:

5.2.1 Technical Capabilities

• CleanCap Technology: Proprietary co-transcriptional capping technology used in majority of approved COVID-19 mRNA vaccines
• Modified Nucleotides: N1-methylpseudouridine and other modifications for reduced immunogenicity and enhanced translation
• Scale Flexibility: Ability to synthesize from 1g to >100g per batch, suitable for single-patient orders
• Quality Systems: ICH Q7 compliant, ISO 9001:2015 certified

5.2.2 New San Diego GMP Facility (2024)

TriLink opened a 32,000 square foot cGMP manufacturing facility in Sorrento Valley, San Diego, specifically designed for mRNA manufacturing. Features include:

• Individual Grade C cleanroom suites
• Comprehensive in-house analytical services
• Support for Phase 2 through commercialization
• Designed for cancer vaccines, gene editing, and protein replacement therapies

5.3 Proposed Partnership Structure

The patient co-owned model proposes a service relationship with CDMOs where:

5.4 Estimated Costs and Timeline

For context, BioNTech's autogene cevumeran is estimated to cost over $100,000 per patient in clinical trial settings. The patient co-owned model achieves comparable costs while preserving patient IP rights.

6. Regulatory Pathways

6.1 Overview of Options

Patient co-owned personalized vaccines can access treatment through several regulatory mechanisms:

6.2 Right to Try Act Considerations

The federal Right to Try Act (2018) provides a pathway for terminally ill patients to access investigational drugs that have completed Phase 1 clinical trials. Key requirements:

• Life-threatening diagnosis: Patient must have a life-threatening disease or condition
• Exhausted approved options: Patient has tried all approved treatment options
• Unable to participate in clinical trial: Or ineligible for available trials
• Drug eligibility: Investigational drug must have completed Phase 1
• Manufacturer consent: Manufacturer can refuse to provide drug

6.3 Physician-Sponsored IND: Recommended Pathway

For patient co-owned personalized vaccines, a physician-sponsored IND (Investigational New Drug application) represents the most robust regulatory approach:

6.3.1 Process

1. Sponsor Identification: Patient's oncologist or institution serves as IND sponsor
2. Pre-IND Meeting: Optional FDA meeting to discuss development plan
3. IND Submission: Chemistry, manufacturing, and controls (CMC); pharmacology/toxicology; clinical protocol
4. FDA Review: 30-day safety review period
5. IRB Approval: Institutional Review Board oversight
6. Treatment Initiation: Upon FDA clearance and IRB approval

6.3.2 CDMO Documentation Requirements

For the physician-sponsored IND, the CDMO would need to provide:

• Certificate of Analysis (CoA) for final product
• Manufacturing batch records
• Stability data (abbreviated for single-patient use)
• Identity, purity, and potency testing results
• Sterility and endotoxin testing
• Characterization of critical quality attributes

6.4 Regulatory Precedents

The FDA has shown flexibility in regulating personalized cancer therapies:

• CAR-T Cell Therapies: Patient-specific manufactured products with expedited approval pathways
• Tumor-Treating Fields: Device-based therapy approved with novel regulatory framework
• Neoantigen Vaccines in Trials: Multiple INDs approved for personalized cancer vaccines

The agency has indicated willingness to work with sponsors on novel personalized medicine approaches that do not fit traditional drug development paradigms.

7. Economic Analysis

7.1 Current Market Economics

7.2 Value Distribution: Current vs. Patient-Owned Model

7.3 Future Economic Scenarios

If personalized neoantigen vaccines prove effective and become standard of care, patient-owned neoantigen sequences could have significant economic value:

7.3.1 Research Licensing

Pharmaceutical companies developing next-generation cancer vaccines may seek access to validated neoantigen-response pairs. Patients with documented vaccine responses could license their sequence data for research.

7.3.2 AI Training Data

Machine learning models for neoantigen prediction require training data linking sequences to clinical outcomes. Patient-owned data could be licensed for AI development with appropriate compensation.

7.3.3 Biobank Contributions

Longitudinal biospecimen collections (blood draws, tumor samples) from vaccine-treated patients represent valuable research resources that patients could contribute on their own terms.

8. Ethical Considerations

8.1 Arguments for Patient Co-Ownership

• Bodily Autonomy: Patients have a fundamental right to control what happens to tissue derived from their bodies
• Informed Consent: True informed consent includes understanding and consenting to economic arrangements
• Equity: Patients should share in value created from their biological contributions
• Research Incentives: Patient ownership could increase willingness to participate in research
• Transparency: Blockchain-verified consent creates accountability

8.2 Potential Concerns

• Access Inequality: Patient-funded vaccines may only be accessible to wealthy individuals
• Regulatory Complexity: Non-standard pathways may increase risk
• Clinical Evidence: Individual treatments outside trials don't contribute to generalizable knowledge
• Quality Assurance: Non-integrated supply chains may have quality risks
• False Hope: Patients may pursue expensive treatments with uncertain benefit

8.3 Mitigation Strategies

The patient co-ownership model addresses these concerns through:

1. Physician Oversight: All treatment decisions made by qualified oncologists
2. Regulatory Compliance: Full adherence to FDA IND requirements
3. GMP Manufacturing: Same quality standards as pharmaceutical-sponsored products
4. Transparent Consent: Clear communication of experimental nature and costs
5. Data Contribution: Patients can opt to contribute outcomes data to research (on their terms)

9. Conclusion and Call to Action

9.1 Summary

Personalized mRNA neoantigen vaccines represent a transformative opportunity in cancer treatment. Phase 1 data demonstrates that these vaccines can induce durable, tumor-specific immune responses that correlate with prolonged survival in pancreatic cancer—one of the deadliest malignancies.

The technology works. The question is: who owns the vaccine derived from your own tumor?

The BioNFT-enabled patient co-ownership model offers an alternative paradigm where:

• Patients retain ownership of their neoantigen sequences
• Chain of custody is verified on blockchain
• Consent is revocable and enforceable
• Manufacturing is performed to GMP standards
• Regulatory pathways provide appropriate oversight
• Future economic value remains with the patient

9.2 Immediate Next Steps

For patients with resectable pancreatic cancer who wish to pursue a co-owned neoantigen vaccine approach:

1. Comprehensive Molecular Profiling: Obtain WES + RNA-seq of tumor and matched normal tissue
2. HLA Typing: Confirm HLA genotype for neoantigen prediction
3. Neoantigen Identification: Engage computational partner for neoantigen prioritization
4. CDMO Engagement: Initiate discussions with GMP mRNA manufacturer
5. Physician Partnership: Identify oncologist willing to sponsor IND
6. BioNFT Infrastructure: Establish blockchain-verified consent and ownership records
7. Treatment Planning: Coordinate vaccine timing with surgical and adjuvant therapy schedule

9.3 Vision

"The broader vision is a platform where patients retain ownership of their neoantigen sequences and chain of custody through manufacturing—essentially democratizing what pharmaceutical companies charge $100K+ to deliver through traditional channels."

This is not an anti-pharma position. Pharmaceutical companies have developed remarkable science that is saving lives. But patients deserve the choice to participate in that value creation as owners, not merely as raw material.

The technology exists. The regulatory pathways exist. The manufacturing capabilities exist. What remains is the will to build a system that respects patient sovereignty over their own biology.

10. References

11. Appendix: Technical Specifications

A.1 Representative Neoantigen Candidates

Based on the clinical case study molecular profile, the following represent potential neoantigen targets:

Note: Actual peptide sequences would be determined through comprehensive neoantigen prediction pipeline including NetMHCpan, MHCflurry, and immunogenicity filtering.

A.2 mRNA Construct Design Template

A.3 Quality Specifications for GMP mRNA

A.4 BioNFT Smart Contract Interface