Flagship Service

Tumor Neoantigen mRNA Vaccine

已验证

8-step end-to-end · From VCF/BAM to mRNA sequence design · Education · Service · Technology

The most mature and competitive pipeline in DiVo Gen²AI's health system. 100% coverage of all dry-lab steps for tumor neoantigen vaccines. This page serves three audiences: patients and public wanting to understand neoantigen vaccines, pharma teams seeking computational service partners, and investors and peers evaluating technical capabilities.

Patients & Public

Read "What is a Neoantigen Vaccine", "5-Step Workflow", "Milestones" below--change your understanding of immunotherapy.

Pharma Teams / Hospitals

Focus on "DiVo's Role", "8-Step Pipeline", "Verified Capabilities", "Sample Reports"--we have deliverables.

Investors / Bioinformatics Peers

Focus on "Three Differentiators", "Benchmarks", "TESLA Baseline", "Glossary"--evaluate technical barriers.

To Patients and Families

Our tumor neoantigen dry-computing pipeline service is a business that works in coordination with medical institutions, not a service directly for individual users and patients. Please contact us through your treating physician at the medical institution where you are being treated. We will not bypass the treating physician to provide any medical opinions about the patient's tumor symptoms and therapies to patients and families. Scientific data and reports should also be obtained and interpreted through your treating physician.

Have a Whole Genome Sequencing Report (VCF)?

If you have your whole genome sequencing report VCF document, we can provide you with non-medical scientific interpretation and analysis reports. Please refer to our general service--Genome Interpretation Report.

What is a Tumor Neoantigen mRNA Vaccine

Every tumor cell carries gene mutations that normal cells don't have. Some of these mutations produce new protein fragments--neoantigens (Neoantigen). They are "fingerprints" left on the surface of tumor cells. The immune system can theoretically identify and eliminate tumors based on these, but in reality the signal is often too weak and escape mechanisms too many, so immune responses fail to initiate.

Neoantigen mRNA vaccines work by encoding patient-specific tumor mutation fragments into mRNA. After being delivered into the body, human cells translate these antigens, actively activating specific T cell responses--like giving the immune system a "wanted poster" to precisely hunt down tumor cells carrying these fingerprints.

This is a completely personalized treatment: each patient's tumor mutation profile is different, so the corresponding vaccine sequence is also different. This is why computational prediction is the lifeline of the entire pipeline--a single tumor sample may produce thousands of candidate peptides, and it's impossible to experimentally validate each one. Algorithms must precisely filter out the few most likely to trigger immune responses.

Why Neoantigens

Only exist in tumor cells, not in normal tissue. Theoretically can be precisely recognized by the immune system without damaging healthy tissue.

Why mRNA

Fast design, short production cycle, no cell culture needed. Naturally fits the "one person, one drug" personalized scenario; sequence is the drug.

Why Computation

Thousands of candidate peptides cannot be individually experimentally validated. Algorithm filtering precision directly determines whether the vaccine can truly activate T cells.

5 Steps of mRNA Vaccines

From tumor sampling to immune activation, a complete personalized vaccine workflow

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1

Sample

Obtain patient tumor tissue samples and normal tissue samples, perform whole exome sequencing (WES)

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2

Identify Targets

Find tumor-specific mutations from sequencing data, screen for neoantigen peptides most likely to activate T cells through MHC binding prediction

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3

Encode mRNA

Encode screened neoantigen peptide sequences into mRNA, optimize codons and UTR sequences for efficient translation in humans

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4

Deliver

Encapsulate mRNA in lipid nanoparticles (LNP) or dendritic cells (DC), inject into patient

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5

Immune Activation

Human cells translate mRNA to produce neoantigen proteins, MHC molecules present them to T cells, initiating specific anti-tumor immune responses

The entire process takes about 4-8 weeks (mainly sequencing + computation + custom mRNA synthesis). Step 2 "Identify Targets" and Step 3 "Encode mRNA"--from sequencing data to mRNA sequence design--are the complete coverage scope of DiVo Gen²AI's computational service.

Neoantigen mRNA Vaccine Development Milestones

From 2017 concept validation to 2025 industrialization acceleration

2017

Sahin team (BioNTech) Nature first reported individualized neoantigen mRNA vaccine clinical results, melanoma patients developed neoantigen-specific T cell responses

Concept validation

2020

Wells team Cell published TESLA benchmark, establishing neoantigen prediction gold standard (608 peptide-MHC)

AUROC benchmark

2023

Moderna mRNA-4157/V940 + Keytruda Phase II significantly prolonged recurrence-free survival, FDA granted breakthrough therapy designation

Combined immune checkpoint

2024

Likon Life LK101 injection received NMPA clinical approval, first domestic AI+personalized neoantigen mRNA vaccine

China first

2025

BioNTech Autogene cevumeran Phase III advancing; Moderna personalized neoantigen vaccine pipeline expanding to multiple cancer types

Industrialization acceleration

DiVo Gen²AI's Role

In the neoantigen mRNA vaccine workflow, we handle all dry-lab steps of "target identification + mRNA design"

In the neoantigen mRNA vaccine workflow, "finding the right targets" and "designing optimal mRNA sequences" are the steps most dependent on computational prediction--impossible to experimentally validate each candidate peptide, algorithms must precisely filter.

  • HLA Typing--determine patient MHC type, wrong typing means everything downstream is wrong
  • Variant Detection & Peptide Generation--extract tumor-specific mutations and candidate peptides from VCF/BAM
  • MHC Binding Prediction + pMHC Structure Validation--from IC50 to atomic-level 3D structure confirmation
  • 5-Dimensional Immunogenicity Scoring--not just affinity, 5 dimensions cross-filtering
  • mRNA Sequence Design + TCR Recognition Validation--from amino acid sequence to deliverable mRNA

We do not produce vaccine entities. We deliver sequence design proposals that can directly enter wet-lab synthesis and clinical filing.

8-Step End-to-End Pipeline

100% coverage of all dry-lab steps · Click steps to view underlying validation

S1

HLA Typing

已验证

OptiType + Polysolver dual-tool cross-validation

4-digit resolution HLA-I typing results

S2

Variant Detection & Annotation

已验证

GATK Mutect2 + VEP + ANNOVAR

Somatic variant list + functional annotation

S3

Peptide Generation

已验证

pVACseq + pVACfuse + ScanNeo2 + NeoGuider

Candidate neoantigen peptides

S4

MHC Binding Prediction

已验证

MHCflurry(14,883 alleles) + MHCnuggets + IEDB API

IC50 min 10.1 nM, 22 high-affinity candidates

S5

pMHC 3D Structure Prediction

已验证

DiVoFold5/Protenix

Atomic-level pMHC structure, pLDDT=95.4, ipTM=0.977

S6

5-Dimensional Immunogenicity Scoring

已验证

MHC affinity 30%+presentation 20%+processing 10%+known immunogenicity 15%+structure score 25%

45 candidates Tier-graded, 17 Tier-1

S7

mRNA Sequence Design

已验证

GEMORNA + RNALens self-tuned + DNAChisel + ViennaRNA

CAI 0.7->0.95, MRL Spearman=0.92

S8

TCR Recognition Validation

已验证

DeepTCR(Recon Acc=0.972) + ProTCR

TCR recognition feasibility assessment

Three Key Differentiators

Capabilities that traditional pipelines lack

3D

pMHC 3D Structure Validation

Traditional pipelines only use IC50 values for binding. DiVo builds atomic-level pMHC 3D structures for each candidate, pLDDT/ipTM validates spatial conformation credibility. 400+ complexes validated at scale.

5X

5-Dimensional Immunogenicity Scoring

Traditional pipelines only use MHC affinity for screening. DiVo adds 5 scoring dimensions--affinity 30%+presentation 20%+processing 10%+known immunogenicity 15%+structure score 25%, higher screening precision.

AI

RNALens Self-Tuned Model

Ribosome loading efficiency prediction for mRNA sequence design--Spearman=0.92, R²=0.87--based on DNABERT-Z 117M three-stage fine-tuning. Not a third-party API call, but part of 560K lines of self-developed code.

Verifiable Engineering Foundation

MetricValueNote
TESLA benchmark AUROC0.698Wells Cell 2020, 608 peptide-MHC
MHC-I allele coverage65IC50 measured min 10.1 nM
MHC-II allele coverage2513 DR + 5 DP + 7 DQ
pMHC structure pLDDT95.4Approaching X-ray crystallography precision
pMHC ipTM0.977Complex overall confidence
RNALens MRL Spearman0.92R²=0.87, self-tuned
mRNA CAI improvement0.7->0.95Codon adaptation index optimization
Large-scale validation400+Complex batch prediction validation
Candidate Tier-1 count17Highest tier among 45 candidates

Top 5 Tier-1 Candidate Neoantigens

Actual validation data, not simulated values

PeptideHLAAntigen SourceIC50 (nM)ScoreTier
LLFGYPVYVHLA-A*02:01HTLV-1 Tax10.1100Tier-1
KVAELVHFLHLA-A*02:01MAGE-A114.4100Tier-1
RMFPNAPYLHLA-A*02:01WT114.3100Tier-1
FLWGPRALVHLA-A*02:01WT113.693Tier-1
IMDQVPFSVHLA-A*02:01NY-ESO-115.993Tier-1

Honest Boundaries

What we can and cannot do, clearly stated

What We Can Do

HLA typing (OptiType + Polysolver dual-tool validation)
Variant detection -> candidate peptide generation -> MHC binding prediction
pMHC atomic-level 3D structure validation (pLDDT=95.4)
5-dimensional immunogenicity scoring + Tier grading
mRNA sequence design (RNALens self-tuned)
TCR recognition feasibility assessment (DeepTCR verified)
Deliver sequence design proposals ready for wet-lab synthesis

What We Don't Do

Do not produce vaccine entities (mRNA synthesis/encapsulation/delivery)
Do not provide clinical diagnostic opinions
Do not do clinical trial design and execution
Do not predict immune response efficacy (lack clinical data)
Do not do LNP delivery system design

Sample Reports Available

Complete 8-step pipeline simulation report, including HLA typing, MHC binding prediction, pMHC structure, immunogenicity scoring, mRNA sequence design full workflow output. 14-page PDF + MD bilingual version.

Industry Market Price Reference

Compiled from public information · Not DiVo pricing · For reference only

Boundary Note: The following are market public reference prices for complete courses of tumor neoantigen mRNA vaccines, covering tumor sequencing, neoantigen screening, mRNA synthesis, delivery systems, personalized production, and all hospital-side costs. DiVo Gen²AI handles the dry-lab computational steps (i.e., the 8-step pipeline on this page), and is not the producer or seller of vaccine entities.

China Domestic
Tumor biopsy/surgical sample whole exome sequencing.Likon Life LK101 injection
Typically multiple doses (4-9 or more), spaced weeks apart.~150K RMB/dose × 7 doses = 600K-1.05M RMB
Often combined with immune checkpoint inhibitors (e.g., PD-1).Advanced solid tumors, Hainan Boao Lecheng
International Reference
Tumor biopsy/surgical sample whole exome sequencing.Moderna mRNA-4157 / BioNTech Autogene
Typically multiple doses (4-9 or more), spaced weeks apart.$100K-300K/course
Often combined with immune checkpoint inhibitors (e.g., PD-1).Melanoma etc., combined with PD-1

Cost Composition and Factors

Personalized SequencingTumor biopsy/surgical sample whole exome sequencing.
Neoantigen ScreeningAI-assisted computational prediction (DiVo's scope).
mRNA SynthesisCustomized sequence production.
Delivery SystemDC cell delivery or LNP lipid nanoparticles.
Treatment CourseTypically multiple doses (4-9 or more), spaced weeks apart.
Combination TherapyOften combined with immune checkpoint inhibitors (e.g., PD-1).
Region & PolicyPioneer zones like Hainan Lecheng may charge earlier; post-launch may have insurance coverage/price reduction.
Future TrendsTechnology maturation + scale-up, costs expected to decrease (cf. COVID mRNA vaccines).

The above are reference data from public reports. Actual costs require consulting specific hospitals/companies and assessing patient indications, safety, and efficacy. Such treatments are mostly self-paid. Consider combining medical advice, clinical trial enrollment (may reduce costs), or financial capacity.

Glossary

10 most common terms in neoantigen mRNA vaccines

Abbr.Full NameTranslationExplanation
NeoantigenNeoantigenNeoantigenAntigen peptides produced by tumor-specific mutations, not expressed in normal tissue, targets for personalized vaccines
MHCMajor Histocompatibility ComplexMajor Histocompatibility ComplexThe "display board" on cell surfaces, presenting intracellular protein fragments to T cells
HLAHuman Leukocyte AntigenHuman Leukocyte AntigenThe name for MHC in humans, determining which peptides can be presented to T cells
IC50Half Maximal Inhibitory ConcentrationHalf Maximal Inhibitory ConcentrationQuantitative metric of MHC-peptide binding affinity, lower is stronger (<50 nM is strong binding)
pMHCpeptide-MHC complexpeptide-MHC ComplexAntigen peptide complex presented by MHC molecules, the target of T cell recognition
pLDDTpredicted Local Distance Difference Testpredicted Local Distance Difference TestProtein structure prediction confidence, >90 is high confidence, >70 is usable
ipTMinterface predicted TM-scoreinterface predicted TM-scoreProtein complex interface interaction confidence, >0.75 is high confidence
CAICodon Adaptation IndexCodon Adaptation IndexmRNA sequence translation efficiency metric, closer to 1 is more efficient
MRLMean Ribosome LoadMean Ribosome LoadDirect measure of mRNA translation efficiency, higher means more protein expression
LNPLipid NanoparticleLipid NanoparticlemRNA delivery vehicle, protecting mRNA and releasing it after entering human cells for translation