Disomotide
Nine amino acids of a melanoma protein, with one letter changed so the immune system would see it
Disomotide is a nine-amino-acid fragment of gp100, a protein that melanoma cells make in quantity. One residue has been swapped, a threonine for a methionine at position 210, which makes the fragment stick far more firmly to the HLA-A2 molecule that presents it to killer T cells. Injected in an oil emulsion, it reliably raises gp100-specific T cells in the blood of most people who receive it. Whether those T cells shrink tumours is the harder question: a randomised phase 3 trial found more responses and longer survival when the peptide was added to high-dose interleukin-2, while three phase 2 trials of the same combination and a later low-dose interleukin-2 trial found nothing. It has never been approved anywhere, and the trials that used it have all finished.
Used in human trials: 100 µg per vaccination site, Days 1 and 15 of each 28-day cycle, at three rotating sites, Subcutaneous injection in oil emulsion (Study: with GM-CSF and a TLR9 agonist, stage IV melanoma) Details ↓
Recommended Dosing
Used in human trials
No manufacturer dose exists for this use: these are amounts given in published trials, not recommendations.
What is it?
Melanoma cells make gp100, a protein of the pigment-making machinery, in far larger amounts than normal skin does. Fragments of it are displayed on the cell surface by HLA molecules, where T cells can read them, and in the early 1990s the fragment running from residue 209 to residue 217 was identified as one that T cells taken out of melanoma tumours recognised. The trouble was that the natural fragment binds HLA-A2 weakly. Changing the second amino acid, a threonine, to methionine strengthens that grip without changing the part the T cell actually reads. The result, IMDQVPFSV, is the molecule now named disomotide, and the one almost every trial used in place of the natural sequence.
As a vaccine it works, in the narrow sense that it does what a vaccine is supposed to do. Mixed into an oil emulsion and injected under the skin every two or three weeks, it raised peptide-specific CD8 T cells in 33 of 35 patients with resected melanoma in one study, and the median frequency of those cells in the blood rose from 0.02% to 0.34% in another. Skin tests turned positive in most vaccinated patients. Six months to two years later the cells were still there, with the surface markings of memory T cells and the ability to divide again on contact with the peptide.
Tumour shrinkage is a different matter. The study that made the peptide famous reported objective responses in 13 of 31 patients given it with high-dose interleukin-2, a rate roughly three times what interleukin-2 alone was expected to achieve. The Cytokine Working Group then ran three phase 2 trials of the same idea in 131 patients and saw an overall response rate of 16.5%, no better than interleukin-2 alone. A cooperative group trial that paired the peptide with low-dose interleukin-2 in 26 patients recorded no responses at all and, awkwardly, no sign that the patients had been immunised.
The one randomised test came last. Between 2000 and 2007, 185 patients with advanced melanoma at 21 American centres were assigned to high-dose interleukin-2 alone or to the peptide in incomplete Freund's adjuvant followed by the same interleukin-2. On blinded central review, 16% of the vaccine group responded against 6% on interleukin-2 alone, progression-free survival was longer by about two weeks, and median overall survival was 17.8 months against 11.1, a difference that fell just short of statistical significance in a trial not designed to measure it. Published in 2011, it was one of the first randomised trials to show a cancer vaccine adding anything to another treatment.
That result has not been repeated, and the drugs the field moved to are different in kind: antibodies that release the brakes on T cells, which work without a vaccine. In the one randomised trial that paired this peptide with such an antibody, adding the vaccine to ipilimumab gave no advantage over the antibody by itself, as the phase 3 report itself notes (PMID 21631324). No trial of disomotide is recruiting, and nothing containing it has been approved by any regulator. It was a research agent supplied to trial sites by the National Cancer Institute, never a product, and the amounts below come from a trial report rather than from any label.
Mechanism of Action
Disomotide does nothing to a tumour by itself. It is a display problem solved: a peptide engineered to sit tightly enough in HLA-A2 to wake up the T cells that can already see gp100 on melanoma cells.
One residue swapped at the anchor
Position 210 of gp100, a threonine, is replaced by methionine. That residue anchors the peptide in the HLA-A*0201 groove rather than facing the T cell, so binding tightens while the face the T cell reads is unchanged (PMIDs 11559721, 9973438).
Given in an oil emulsion
The peptide is emulsified in incomplete Freund's adjuvant and injected under the skin, which holds it at the site and draws immune cells in. The emulsion's own composition changed the response it produced (PMID 20551834), and mixing two peptides into one emulsion suppressed the response to this one (PMID 16531823).
CD8 T cells, in quantity
Vaccination raises peptide-specific CD8 T cells in most recipients, with effector and memory phenotypes that persist for a year or more (PMIDs 12697882, 14760090, 19318471).
Only HLA-A2, and only some T cells see tumours
Presentation needs HLA-A*0201, so trials enrolled only patients with that type. Many of the clones raised recognise the modified peptide but not melanoma cells, and avidity for the natural peptide is what tracks tumour reactivity (PMIDs 9973438, 10404430, 17589294).
Published Research
Sixteen human studies, read from their PubMed records, with the open full texts of the phase 3 trial and the TLR9-adjuvant trial. All of them gave this peptide to people: the trials that measured tumour response, the adjuvant comparisons that measured immune response, and two laboratory studies of T cells grown from vaccinated patients. Ten are carded although their titles name the condition, the adjuvant or gp100 alone, because their abstracts name the modified peptide as the agent given.
Phase 3: the vaccine added to high-dose interleukin-2
185 patients with HLA-A*0201 and advanced melanoma were randomised to high-dose interleukin-2 alone or to the peptide in Montanide ISA-51 once per cycle followed by the same interleukin-2. Centrally reviewed response was 16% against 6%, progression-free survival 2.2 against 1.6 months, and median overall survival 17.8 against 11.1 months. Arrhythmias, mostly transient tachycardia, were more common in the vaccine group.
Three phase 2 trials of the same combination
The Cytokine Working Group gave the peptide in weeks 1, 4, 7 and 10 with high-dose interleukin-2 on three different schedules. Among 121 assessable patients of 131 enrolled, 16.5% responded overall, by trial 23.8%, 12.5% and 12.8%, with 11 complete responses. None of the blood immune measures predicted who benefited, and the authors concluded the combination had not reproduced the earlier 42%.
Phase 2 with low-dose interleukin-2
26 patients with advanced melanoma received the peptide every three weeks with low-dose subcutaneous interleukin-2. There were no objective responses, no grade 4 toxicity, and neither ELISPOT nor tetramer assays showed convincing induction of peptide-reactive T cells, which the authors read as a warning about giving peptides alongside interleukin-2.
684 patients treated at one centre over 20 years
In a review of consecutive patients given high-dose interleukin-2 with or without various vaccines, response rates were 13% without a vaccine and 16% with one. Patients who received this particular peptide responded at 22% against 12.8% for interleukin-2 alone and 13.8% for other vaccines. Responding was strongly associated with surviving past four years.
Adjuvant vaccination after resection: how often to inject
30 patients with resected stage I-III melanoma were randomised to vaccination every two weeks or every three weeks for six months. Peptide-specific CD8 T cells rose in 28 of 29 patients, with the median frequency climbing from 0.02% to 0.34%; eight patients exceeded 1%. The two schedules performed alike, and concurrent interferon did not block the response.
Effector and memory T cells after six months of vaccination
35 patients with resected stage I-III melanoma were vaccinated repeatedly over six months. Tetramer-positive CD8 T cells rose significantly in 33 of 35, most carrying effector or effector-memory markings, and specific memory cells were still present in blood taken 12 to 24 months later. Some patients' expanded cells failed to produce interferon gamma, which the authors took as functional anergy.
Did the T cells recognise real tumour cells?
In vaccinated patients with resected stage I-III disease, peptide-reactive T cells were found in 79% and tumour-reactive T cells in 66% of those examined. Patients fell into three groups: some whose T cells saw only the modified peptide, some that also saw the natural one, and some whose cells recognised melanoma cell lines. Low-avidity cells that needed peptide added to the tumour cells were common.
T cells in the lymph node that drained the injection
After two or three vaccinations, sentinel nodes draining both the primary tumour and the vaccine site were removed and compared with blood. Node and blood frequencies of specific CD8 T cells were similar and resembled those of virus-specific memory cells; node cells divided better, while circulating cells had higher functional avidity and stronger degranulation responses to tumour cells.
With a TLR9 agonist and local GM-CSF
22 patients with stage IV melanoma received this peptide with MART-1 and tyrosinase peptides, each at 100 µg per site with GM-CSF and the TLR9 agonist PF-3512676 in oil, on days 1 and 15 of 28-day cycles. Nine of 20 evaluable patients mounted an ELISPOT response; there were two partial responses and eight patients with stable disease, and no grade 3 or worse regimen-related toxicity.
Interleukin-12 with alum against interleukin-12 with GM-CSF
60 patients with resected high-risk melanoma were randomised to three adjuvant combinations beside this peptide and two others. Six-month immune responses to gp100 were far more common with interleukin-12 plus alum (15 of 19 and 19 of 20) than with interleukin-12 plus GM-CSF (4 of 21). Response to the MART-1 peptide was associated with longer relapse-free survival.
Interleukin-12 as an adjuvant after resection
48 patients with resected stage III or IV melanoma received this peptide and a tyrosinase peptide in incomplete Freund's adjuvant, with or without interleukin-12. Skin tests turned positive to the gp100 peptide in 34 of 40 patients and to tyrosinase in none; 33 of 38 responded by ELISA and 37 of 42 by tetramer. Toxicity stayed at grade 1 or 2 apart from transient grade 3 events.
GM-CSF as an adjuvant in resected stage II melanoma
48 patients were randomised to the same two peptides in adjuvant with or without five days of GM-CSF. Immune responses appeared in 34 of 39 by ELISA and 37 of 42 by tetramer, higher in the GM-CSF arm, and spreading of the response to MART-1 epitopes was seen in 10 patients. Skin tests turned positive to gp100 in 17 of 40 and to tyrosinase in one.
Mixing peptides in one emulsion weakened the response
Two sequential trials in 31 and 33 patients at high risk of recurrence gave this peptide and a tyrosinase peptide either emulsified separately and injected at two sites or emulsified together at one. Injected separately, reactivity to gp100 was strong; injected together, it dropped sharply while the tyrosinase response improved.
The adjuvant's own ingredients mattered
When concern about prion contamination moved Montanide ISA-51 from beef-derived to olive-derived oleic acid in 2006, patients vaccinated with the same peptide in the newer emulsion generated far fewer reactive T cells on both ELISPOT and sensitisation assays, and had milder skin reactions. The authors raised it as a problem for the trials then using the olive-derived adjuvant.
Many of the T cells raised could not see melanoma cells
T-cell clones grown from three vaccinated patients were compared with clones from tumour-infiltrating lymphocytes. Every clone from the tumour recognised melanoma cell lines, while only 3 of 20 clones from vaccinated patients' blood did; 5 of 20 recognised only the modified peptide. Vaccination had expanded a mixed repertoire, much of it blind to the real antigen.
Avidity predicted which clones recognised tumours
Clones from three patients treated for metastatic melanoma with the modified peptide varied widely in how tightly they responded to it and in whether they killed melanoma cell lines. A clone's avidity for the natural peptide, not the modified one, predicted its tumour reactivity, which the authors read as a caution for both vaccination and cell-transfer therapy.
Dosing Data
The peptide was given only inside clinical trials, by trial staff, as a series of injections under the skin. Most published reports describe the schedule but not the amount; the figure below is one that a trial's full text states. There is no approved dose and no product.
Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
What a Buyer Needs to Know
What is sold, how it is mixed, stored and taken, and what is known about its safety, quality and legal status. Each part names its source. Where we have none, it says unknown.
What is sold
Unknown: we hold no label and no published test that says what forms or vial sizes Disomotide is sold in. A vial's own label is a seller's claim, not a source.
Mixing a vial: a worked example
An arithmetic example, not a recommendation: a 5 mg vial mixed with 2 mL of bacteriostatic water holds 2,500 mcg per mL, so every 10 units on a U-100 insulin syringe hold 250 mcg. 100 µg, the first amount in the “Study: with GM-CSF and a TLR9 agonist, stage IV melanoma” row (100 µg per vaccination site) is 4.0 units (0.040 mL). If your vial or water differ, the numbers change: use the reconstitution calculator.
Source: dose: Used in human trials, PMID 22495394 (Dosing Data below); vial and water: the calculator's default example, not a vial size we have a source for.
Storage before and after mixing
Unknown: no label or published stability study on file says how to store Disomotide, before or after mixing. The mixing guide sets out the general rules, with their sources: keep a mixed vial in the fridge, and use it promptly, as the bacteriostatic water label says of any drug dissolved in it. The 28 days often quoted is the limit for an opened multiple-dose vial from a manufacturer, an outer limit set for sterility, not a time a mixed solution has been shown to keep. Nobody has published how long Disomotide stays intact once mixed.
How it is taken
As it was given in human studies: Subcutaneous injection in oil emulsion (Days 1 and 15 of each 28-day cycle, at three rotating sites; Study: with GM-CSF and a TLR9 agonist, stage IV melanoma).
For injection technique, sites and needle disposal, see the mixing guide.
Source: Used in human trials: the route and frequency of each row in Dosing Data below.
What to expect, and when
How long it stays in the body: not established by a measurement cited on this entry.
How long the doses were given: Study: with GM-CSF and a TLR9 agonist, stage IV melanoma: Up to 13 cycles.
When effects appear: unknown; no source on this page gives a time to effect for Disomotide. Results reported in the studies are under Published Research.
Source: Used in human trials, the duration of each row in Dosing Data below.
Side effects, and when to stop or get help
From the Side Effects section: Pain, redness and granuloma formation at the injection site, the commonest events in the adjuvant trials (PMIDs 11559721, 12491520); Fever and lethargy of mild or moderate grade (PMIDs 11559721, 12491520); Transient arrhythmias, mostly sinus tachycardia and supraventricular events, more frequent when the peptide was added to high-dose interleukin-2 (PMID 21631324); The toxicity of high-dose interleukin-2 itself, which dominated the phase 3 trial in both groups (PMID 21631324); Grade 3 colitis, visual change and headache in a trial that also gave interleukin-12, resolving when the interleukin-12 was stopped and the peptide continued (PMID 17200357); No regimen-related grade 3 or worse events in the trial combining it with GM-CSF and a TLR9 agonist (PMID 22495394). Full list and cautions ↓
When to stop or get help: unknown; no label or trial on file sets rules for stopping Disomotide. Treat a severe or unexpected reaction as a reason to stop and see a doctor.
Source: the Side Effects section below (“From the human trials above”).
Interactions
Unknown: a PubMed search for human interaction studies of Disomotide (reviewed 2026-11-03) found none. Unknown is not the same as safe to combine.
Every peptide's record, with its source: the interaction matrix.
Checking what you bought
Unknown: no published independent test of Disomotide products is in our lab-results database yet, so how products sold under this name measure up is not known.
To read a certificate of analysis, paste it into the COA decoder; it checks the measured mass against Disomotide's expected mass, 1,035.2 Da, from this entry's molecular data. Trust & Verification explains what independent testing can and cannot show.
Legal status
US: Not FDA Approved (Never approved: Drugs@FDA (openFDA) holds no application for disomotide or a gp100 peptide vaccine (searched November 3, 2026), and ChEMBL records a highest clinical phase of 2). Sport: Prohibited (S0 catch-all).
Country by country ↓ · Regulatory tracker
Source: this entry's approval status and the WADA Prohibited List, as in Legal Status below.
Side Effects & Contraindications
Reported Side Effects
From the human trials above. Most of them gave the peptide beside interleukin-2, an adjuvant or another cytokine, so side effects belong partly to those.
Contraindications & Cautions
No label exists, so there are no formal contraindications. These are the limits the trials themselves worked within.
Legal Status
Disomotide is an investigational research agent with no marketing approval anywhere. It was distributed to trial sites under an investigational new drug application held by the National Cancer Institute.
Frequently Asked Questions
?What is disomotide?
It is a nine-amino-acid piece of the melanoma protein gp100, running from residue 209 to 217, with the threonine at position 210 changed to methionine. The change makes it bind the HLA-A2 molecule more tightly, which is what lets it stimulate T cells well enough to work as a vaccine.
?Why change an amino acid at all?
The natural fragment binds HLA-A2 weakly, so little of it is displayed and the immune response is feeble. Position 210 points into the HLA groove rather than at the T cell, so swapping it strengthens the hold without changing what the T cell sees.
?Did it shrink tumours?
On its own, barely. Added to high-dose interleukin-2 in a randomised phase 3 trial it roughly doubled the response rate, from 6% to 16%, and overall survival favoured the vaccine group without reaching significance. Three earlier phase 2 trials of the same combination and a low-dose interleukin-2 trial found no such benefit.
?Is it the same as ovemotide?
No. Ovemotide is a different gp100 epitope, residues 280 to 288 with valine at 288, sequence YLEPGPVTV. The two were sometimes tested in the same multipeptide vaccines, but they are separate molecules and the studies on this page are studies of disomotide.
?Why did development stop?
Interest moved to checkpoint antibodies, which work without a vaccine. In the trial that paired this peptide with ipilimumab, adding it gave no advantage over the antibody alone (reported in the phase 3 paper, PMID 21631324), and no trial of the peptide is recruiting now.
?Can I get it?
No. It was a research agent supplied to trial sites, never a product, and nothing containing it is approved or sold.
References
- [clinical-trial] Schwartzentruber DJ, et al. "gp100 peptide vaccine and interleukin-2 in patients with advanced melanoma." N Engl J Med, 2011;364(22):2119-27. PMID: 21631324.
- [clinical-trial] Sosman JA, et al. "Three phase II cytokine working group trials of gp100 (210M) peptide plus high-dose interleukin-2 in patients with HLA-A2-positive advanced melanoma." J Clin Oncol, 2008;26(14):2292-8. PMID: 18467720.
- [clinical-trial] Roberts JD, et al. "Phase 2 study of the g209-2M melanoma peptide vaccine and low-dose interleukin-2 in advanced melanoma: Cancer and Leukemia Group B 509901." J Immunother, 2006;29(1):95-101. PMID: 16365605.
- [clinical-trial] Tarhini AA, et al. "Safety and immunogenicity of vaccination with MART-1 (26-35, 27L), gp100 (209-217, 210M), and tyrosinase (368-376, 370D) in adjuvant with PF-3512676 and GM-CSF in metastatic melanoma." J Immunother, 2012;35(4):359-66. PMID: 22495394.
- [clinical-trial] Hamid O, et al. "Alum with interleukin-12 augments immunity to a melanoma peptide vaccine: correlation with time to relapse in patients with resected high-risk disease." Clin Cancer Res, 2007;13(1):215-22. PMID: 17200357.
- [clinical-trial] Lee P, et al. "Effects of interleukin-12 on the immune response to a multipeptide vaccine for resected metastatic melanoma." J Clin Oncol, 2001;19(18):3836-47. PMID: 11559721.
- [clinical-trial] Weber J, et al. "Granulocyte-macrophage-colony-stimulating factor added to a multipeptide vaccine for resected Stage II melanoma." Cancer, 2003;97(1):186-200. PMID: 12491520.
- [clinical-trial] Smith JW 2nd, et al. "Adjuvant immunization of HLA-A2-positive melanoma patients with a modified gp100 peptide induces peptide-specific CD8+ T-cell responses." J Clin Oncol, 2003;21(8):1562-73. PMID: 12697882.
- [pubmed] Walker EB, et al. "gp100(209-2M) peptide immunization of human lymphocyte antigen-A2+ stage I-III melanoma patients induces significant increase in antigen-specific effector and long-term memory CD8+ T cells." Clin Cancer Res, 2004;10(2):668-80. PMID: 14760090.
- [pubmed] Meijer SL, et al. "Induction of circulating tumor-reactive CD8+ T cells after vaccination of melanoma patients with the gp100 209-2M peptide." J Immunother, 2007;30(5):533-43. PMID: 17589294.
- [clinical-trial] Walker EB, et al. "Characterization of the class I-restricted gp100 melanoma peptide-stimulated primary immune response in tumor-free vaccine-draining lymph nodes and peripheral blood." Clin Cancer Res, 2009;15(7):2541-51. PMID: 19318471.
- [clinical-trial] Rosenberg SA, et al. "Altered CD8(+) T-cell responses when immunizing with multiepitope peptide vaccines." J Immunother, 2006;29(2):224-31. PMID: 16531823.
- [clinical-trial] Rosenberg SA, et al. "Different adjuvanticity of incomplete freund's adjuvant derived from beef or vegetable components in melanoma patients immunized with a peptide vaccine." J Immunother, 2010;33(6):626-9. PMID: 20551834.
- [pubmed] Smith FO, et al. "Treatment of metastatic melanoma using interleukin-2 alone or in conjunction with vaccines." Clin Cancer Res, 2008;14(17):5610-8. PMID: 18765555.
- [pubmed] Clay TM, et al. "Changes in the fine specificity of gp100(209-217)-reactive T cells in patients following vaccination with a peptide modified at an HLA-A2.1 anchor residue." J Immunol, 1999;162(3):1749-55. PMID: 9973438.
- [pubmed] Dudley ME, et al. "Antitumor immunization with a minimal peptide epitope (G9-209-2M) leads to a functionally heterogeneous CTL response." J Immunother, 1999;22(4):288-98. PMID: 10404430.
- [pubmed] Rosenberg SA, et al. "Immunologic and therapeutic evaluation of a synthetic peptide vaccine for the treatment of patients with metastatic melanoma." Nat Med, 1998;4(3):321-7. PMID: 9500606.
- [pubmed] Butterfield LH, et al. "Immune Correlates of GM-CSF and Melanoma Peptide Vaccination in a Randomized Trial for the Adjuvant Therapy of Resected High-Risk Melanoma (E4697)." Clin Cancer Res, 2017;23(17):5034-5043. PMID: 28536308.
- [registry] ClinicalTrials.gov API v2, read November 3, 2026: a search for intervention 'gp100:209-217(210M)' returns 19 studies, 16 completed, one terminated (NCT00303836) and one withdrawn (NCT00357461), none recruiting. They include NCT00019682 (phase 3, 185 enrolled, aldesleukin with or without the vaccine), NCT00059475 (phase 2, 138 enrolled), NCT00273910 (phase 2, 104 enrolled, adjuvant comparison) and NCT01176461 (phase 1, 127 enrolled, several class I peptides with escalating doses of an anti-PD-1 antibody). A search for 'disomotide' returns none. https://clinicaltrials.gov/study/NCT00019682
- [other] ChEMBL CHEMBL263429 (disomotide; synonyms 'gp100:209-217(210M) peptide', MPS-22): C47H74N10O14S, 1035.23 g/mol, highest clinical phase 2. Read November 3, 2026. https://www.ebi.ac.uk/chembl/compound_report_card/CHEMBL263429/
- [other] PubChem CID 657090 (disomotide): C47H74N10O14S, 1035.2 g/mol, matching the formula and mass computed from IMDQVPFSV. Read November 3, 2026. https://pubchem.ncbi.nlm.nih.gov/compound/657090
- [other] US FDA, Drugs@FDA (openFDA drugsfda endpoint), searched November 3, 2026: no application for disomotide or for a gp100 peptide vaccine.
Sources & Citations
Every study on this page was read from its PubMed record on November 3, 2026, two of them in full text from PubMed Central. Registered trials come from the ClinicalTrials.gov API, regulatory status from Drugs@FDA, and the molecular record from ChEMBL and PubChem, all read the same day. Other gp100 epitopes, other peptides given in the same vaccines and the cytokines and antibodies combined with it are named only for context. Grey Peptides sells nothing and links to no vendor.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.