Cancer-testis antigen design

Designing a cancer-testis antigen vaccine

Our aim is to design one vaccine antigen that targets cancer-testis antigens (CTAs) expressed across cancers responsible for the most deaths worldwide. We select CTA-specific protein regions with MS-observed MHC ligands, exclude shared non-CTA sequences and verified normal-tissue ligands, and assemble segments to broaden HLA coverage while limiting construct length and predicted junctional binding.

Explore the selected proteins
The complete antigen

Each color follows one protein through the construct. Select a segment to explore its evidence.

What strict and loose actually allow

These are curated tissue-expression definitions. They do not establish that a tissue is immune privileged or that targeting it is safe.

Strict · core reproductive tissues

Testis, ovary and placenta. These tissues enter the core reproductive RNA fraction.

Loose · extended reproductive tract

The strict tissues plus cervix, endometrium, epididymis, fallopian tube, prostate, seminal vesicle and vagina.

Neither RNA numerator includes breast or lactating breast. OncoRef applies its curated reproductive-fraction and protein-expression rules, including exceptions; these are not absolute zero-expression gates. Thymus remains in the default RNA fraction denominator but is excluded from the somatic maximum and reproductive protein flag. Protein restriction conventions also use broader reproductive tissue labels. Each definition changes which protein isoforms count as non-CTA background.

CT83 · membership, evidence and selection

The proteins that made it through

Every target contributes at least one contiguous, CTA-specific piece containing an observed MHC ligand.

Selected proteins and retained evidence. Select a protein for details.
PiecesPeptide–HLA pairsHLA alleles

Identical full protein sequences share one target. Peptides shared between different targets count once in the overall total.

View the full protein sequence funnelFull, CTA-specific, MS-supported, padded and assembled sequence lengths for each protein

Which cancers drive the priority?

A protein scores higher when it is highly expressed in more samples from cancers that account for more deaths worldwide.

What “p95 occurrence” means

The percentage of cancer samples in which a protein ranks in the top 5% of expression within that sample.

For example, 30% means the protein reaches that expression rank in 30 out of 100 measured samples. It does not mean the vaccine covers 30% of patients.

Priority contribution =
world mortality share ×
p95 sample prevalence

The ranking adds these contributions across cancer categories. Incidence is shown for context and is not multiplied into the score.

Compare every protein across the cancer categoriesHeatmap of p95 sample prevalence with global mortality shares for each cancer category

Observed peptides, carefully assigned presenters

Mass spectrometry establishes that a peptide was observed. HLA restriction may be measured or inferred from binding predictions.

How the retained evidence is supported

Counts are distinct peptide–HLA pairs, assigned their strongest available evidence tier. Multiple alleles can share one observed peptide.

The inclusion rule

A longer observed peptide does not support an unobserved shorter sequence. HLA reach uses measured and inferred assignments as explicitly labeled; MS observations do not validate predicted HLA restrictions or establish T-cell recognition.

Retained peptide evidence by panel allele
HLA alleleDistinct peptidesProteinsMonoallelic MSTyped-sample inferenceUntyped inference

What each addition contributes

Compare allele-carrier reach, cancer-expression bounds and observed ligand evidence as proteins and segments are added.

Cumulative estimated HLA reach and mortality/incidence-weighted expression union bounds
Proteins enter in mortality-priority order. The shaded cancer bands reflect unknown patient overlap, not statistical confidence intervals.
Distinct observed MS peptides by restriction evidence and peptide-HLA pairs versus construct prefix length
Segments enter in final construct order. Prefixes include preceding methionine/linkers; they are not separately optimized vaccines. Each exact peptide is counted once and colored by its strongest available HLA evidence.
Panel allele frequencies and retained peptide counts by measured and inferred restriction evidence
Allele frequency is the proportion of allele copies. Individual carrier reach accounts for two copies per locus. A missing CIWD frequency is marked with a dagger.

Explore a cumulative protein panel

Cancerp95 expression union boundsUnknown protein measurements

HLA reach and cancer-expression coverage are separate calculations. Their curves are not multiplied into a clinical coverage claim. Expression cohorts are not a representative worldwide patient sample, and antigen processing, tumor HLA loss and immune responses are not included. The cancer axes use global burden shares without renormalizing the represented cancer subset.

Why choose regions rather than the whole protein?

Compare the retained native sequence with shared-protein regions and actual peptide observations from cancer and normal samples.

Full native protein map showing specificity intervals, chosen segments and MS observation sources

Exact MS peptide / native positionSample typeTissue / disease / cellsHLA restriction evidenceRetained?Study

“Cancer-only in this corpus” means no noncancer observation was found in the supplied query, not that a peptide is cancer-specific. Absence of an MS hit is not evidence of absence. Normal-tissue hits in retained regions remain visible and require review. Peptides shared among genes cannot identify their source gene from sequence alone. MS supports observation, not T-cell recognition or vaccine safety.

A single, contiguous antigen

Protein segments stay contiguous. Terminal context and their order are adjusted to reduce predicted junctional binding.

View the complete annotated construct mapPosition and native coordinates of every retained segment in the complete antigen

From cancer priorities to retained sequence

The same biological rules apply to both definitions.

  1. Rank protein identities

  2. Keep CTA-specific regions

    Remove every residue covered by an 8-amino-acid sequence found in an independent non-CTA proteoform. Retain the remaining regions as contiguous stretches.

  3. Require observed ligand evidence

  4. Assemble within the length limits

How to interpret this design

This is a research antigen design. Expression ranking, normal-tissue restriction, observed peptides and binding predictions do not establish clinical efficacy or safety. Remaining junctional predictions need review and experimental validation.

Mortality and incidence values are shares of reference totals. Absolute counts are not available for every category. Cancer sample overlap and clinical patient coverage are not calculated.

Where the data come from

Carrier calculations follow the locus-aware assumptions described by Bui and colleagues. The worldwide donor-registry frequency reference is CIWD 3.0, as tabulated in Table A2 of Lőrincz and colleagues. These donors are a frequency proxy, not a census-weighted worldwide population.

Take the details with you

Download sequences, scientific figures and the complete tables for the selected definition.