gp100 peptide vaccine

gp100:209–217(210M), g209-2M, gp100 209-2M, g280-9V, MDX-1379 (the gp100 vaccine used as the control arm in the ipilimumab registration trial); parent protein gp100 / PMEL / premelanosome protein

Oncology & imaging

Awaiting medical reviewEN ES DE FR PT ZH+ Follow for updates

Note on this profile. The gp100 peptide vaccine is an investigational cancer immunotherapy that has only ever been given inside clinical trials, under oncology supervision, usually alongside high-dose interleukin-2 in an intensive-care-capable unit. It is not a product anyone obtains or uses outside a trial, and nothing here describes self-preparation.

Summary

Class: Short synthetic HLA-A*02:01-restricted class I peptide epitopes (9 amino acids) from the melanocyte differentiation antigen gp100, most often the anchor-modified analogue gp100:209–217(210M), emulsified in the water-in-oil adjuvant Montanide ISA-51
Mechanism: Presents a melanoma-associated peptide to the immune system in a strongly adjuvanted depot so that CD8+ "killer" T cells specific for gp100-bearing melanoma cells expand
Routes studied: Subcutaneous or intradermal injection of a peptide-in-adjuvant emulsion, in repeated cycles; given with high-dose IL-2 in the pivotal trial
Half-life: Not meaningful as a pharmacokinetic figure — the peptide is cleared within minutes to hours, while the adjuvant depot and the resulting T-cell response are what persist
Storage: Clinical-trial product prepared and emulsified by a hospital pharmacy immediately before use; refrigerated vialled peptide
Regulatory status: Not approved anywhere, in any country, for any indication. See region table

Doses are as reported in studies or by the community — never recommendations.

1What it is

gp100 (also called PMEL) is a normal protein inside the pigment-making machinery of melanocytes. Melanoma cells, being descended from melanocytes, usually carry a great deal of it, so fragments of gp100 appear on their surface bound to HLA class I molecules. In the 1990s researchers at the US National Cancer Institute identified the nine-amino-acid fragment at positions 209–217 as one of the pieces that human T cells recognise, and then improved it: swapping a single residue (threonine to methionine at position 210) makes the peptide bind HLA-A*02:01 much more tightly, producing the "210M" anchor-modified analogue used in almost all trials.

The vaccine is therefore a very simple product — one short synthetic peptide mixed with an oil adjuvant — and it became the most-tested peptide cancer vaccine of the pre-checkpoint-inhibitor era. It only works in people who carry HLA-A*02:01, roughly 40–50% of people of European ancestry and fewer in most other populations.

2How it's thought to work

A short class I peptide injected in a Montanide depot is taken up and presented by antigen-presenting cells at the injection site and draining lymph node.

gp100-specific CD8+ T cells, which already exist at low frequency in most people, expand and acquire effector function.

Those T cells circulate and, where they reach a tumour, kill melanoma cells displaying the same peptide.

High-dose IL-2 was added in the pivotal trial as a systemic T-cell growth factor, on the reasoning that the vaccine supplies the specificity and IL-2 supplies the expansion.

A nine-amino-acid fragment of the melanoma antigen gp100 with an adjuvant. Presented on a dendritic cell, it trains cytotoxic T cells to recognise melanocytes carrying it.Schematic — not to scale

A persistent problem with short class I peptides is that they can be presented directly by cells that are not professional antigen-presenting cells, which can tolerise rather than activate T cells. This is one of the main reasons the field has moved to longer synthetic peptides (see profile 238).

3What the research shows

Metastatic melanoma, with high-dose IL-2

A randomised phase 3 trial in 185 patients with HLA-A*02:01-positive advanced melanoma compared gp100:209–217(210M) in Montanide plus high-dose IL-2 against high-dose IL-2 alone. The vaccine arm had a higher objective response rate (16% vs 6%) and longer progression-free survival (about 2.2 vs 1.6 months), with a median overall survival difference that was suggestive but not the primary endpoint (Schwartzentruber 2011, NEJM). This remains the only positive randomised trial of any peptide cancer vaccine in melanoma. It has been criticised because the control arm's response rate was lower than historical IL-2 experience, and because the absolute gains were small. [1]

Graded A (negative)

Metastatic melanoma, as a single agent

In the trial that registered ipilimumab, gp100 peptide vaccine served as the active comparator. Patients given gp100 alone had a median overall survival of about 6.4 months, versus about 10.1 months with ipilimumab; adding gp100 to ipilimumab did not improve on ipilimumab alone (Hodi 2010, NEJM). In other words, the largest randomised experience with this vaccine showed no benefit from it, and it is now generally read as a near-placebo control. [2]

Adjuvant and earlier-stage settings

Multiple single-arm and small randomised studies in resected stage II–III melanoma reported immune responses in a majority of vaccinated patients, with no convincing recurrence-free survival benefit. T-cell response frequency and clinical outcome were repeatedly found to be poorly correlated.

gp100 as a target by other means

The antigen itself has been validated: tebentafusp (Kimmtrak), a gp100-directed bispecific T-cell engager rather than a vaccine, improved overall survival in metastatic uveal melanoma and is approved in the US, EU and UK. This is worth stating plainly — the target is real; the short-peptide vaccine approach to it was what underperformed.

4Reported side effects and interactions

Literature-reported

injection-site reactions are near-universal with Montanide ISA-51 — erythema, induration, and sterile granulomas or ulcerating nodules that can persist for months. Flu-like symptoms, fatigue and low-grade fever. Vitiligo and uveitis have been reported, consistent with an immune response against normal melanocytes. In the IL-2 combination trials the great majority of serious toxicity came from IL-2 (hypotension, capillary leak, renal impairment), not from the peptide.

Community-reported

Community use: essentially none documented. This is a trial-only product; there is no grey market and no self-administration literature.

Theoretical. autoimmunity directed at normal pigmented tissue — skin, eye, inner ear — is the mechanistically expected risk.

Interactions. high-dose IL-2 (studied, additive toxicity from IL-2); checkpoint inhibitors (studied with ipilimumab, no added benefit); systemic corticosteroids would be expected to blunt the vaccine response.

Markers researchers commonly monitor

Trial protocols, not community practice:

Marker	Why it's watched
*HLA-A02:01 genotype**	not a monitoring marker but a gating test; the vaccine cannot work without it.
gp100-specific CD8+ T-cell frequency (ELISpot, intracellular cytokine staining, tetramer/dextramer flow)	the pharmacodynamic readout of whether the vaccine did anything immunologically. Repeatedly shown to correlate poorly with tumour response.
Tumour imaging by RECIST / irRECIST	the only outcome that has ever mattered in these trials.
LDH and standard melanoma prognostic labs	baseline prognosis dominates outcome in advanced melanoma and confounds small single-arm studies.
Thyroid function, morning cortisol, slit-lamp examination	screening for immune-related autoimmunity, especially when combined with a checkpoint inhibitor.
CBC, CMP, renal function	driven mainly by the IL-2 or chemotherapy given alongside.
Injection-site examination at each visit	Montanide granulomas are common and occasionally need intervention.

Free for everyone. Safety information is never behind a paywall.

5Formulation and administration context

Supplied to trial sites as sterile or solution-phase peptide, emulsified by hospital pharmacy with Montanide ISA-51 into a stable water-in-oil emulsion immediately before injection, then given subcutaneously or intradermally in repeated cycles over months. Emulsion quality is a real variable: an incompletely emulsified preparation does not form the depot the mechanism depends on. HLA-A*02:01 typing is a prerequisite for eligibility. There is no outpatient, self-prepared or compounded version of this product, and no dose calculation that would be appropriate to publish.

6Commonly studied alongside

High-dose interleukin-2; ipilimumab; Montanide ISA-51 and GM-CSF as adjuvants; tyrosinase and MART-1 peptides in multi-epitope melanoma vaccines. Conceptually related: Nelipepimut-S (profile 232), IMA901 and multi-peptide vaccines (profile 236), neoantigen peptide vaccines (profile 238).

Informational cross-links. Not stack recommendations.

7Regulatory status by region

Region	Status (checked —)
United States	Not FDA-approved; investigational only. The gp100 antigen is targeted by an approved product (tebentafusp), which is a different class of drug
European Union	Not authorised
United Kingdom	Not licensed
Australia	Not approved
South Africa	Not registered with SAHPRA
Sport	Not listed by WADA; no plausible performance application

8Open questions

Did the single positive IL-2 combination trial reflect a real vaccine effect, or an under-performing control arm?
Can short class I peptides ever avoid inducing T-cell tolerance, or is the longer-peptide/mRNA approach strictly better?
Does any role remain for gp100 peptide vaccination as a priming step before checkpoint blockade or adoptive cell therapy?

9References

1Schwartzentruber DJ et al. (2011). gp100 peptide vaccine and interleukin-2 in patients with advanced melanoma. New England Journal of Medicine. PubMed · DOI
2Hodi FS et al. (2010). Improved survival with ipilimumab in patients with metastatic melanoma. New England Journal of Medicine. PubMed · DOI
3Rosenberg SA et al. (1998). Immunologic and therapeutic evaluation of a synthetic peptide vaccine for the treatment of patients with metastatic melanoma. Nature Medicine. PubMed · DOI
4Parkhurst MR et al. (1996). Improved induction of melanoma-reactive CTL with peptides from the melanoma antigen gp100 modified at HLA-A0201-binding residues. Journal of Immunology*. PubMed
5Nestle FO et al. (2005). Vaccination of melanoma patients with peptide- or tumour lysate-pulsed dendritic cells — review context. Nature Medicine (review). PubMed
6Nathan P et al. (2021). Overall survival benefit with tebentafusp in metastatic uveal melanoma. New England Journal of Medicine. PubMed · DOI

References are being resolved to PubMed/DOI identifiers; links search PubMed for the citation until then.

10Community

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Self-reported side effects Phase 2

Not enough data yet. 0 of the 50 members needed have logged this compound for 4+ weeks. We don't show anything below 50, so no one can be identified.

11Page history

31 Oct 2026Profile published — awaiting medical review

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