ALT-801

Fusion ProteinRx: InvestigationalCompound: Investigational

Also known as: ALT-801, ALT801, c264scTCR/IL-2, IL-2‑fusion peptide, TCR-IL2 fusion protein

Educational Only — Not medical advice. Consult a qualified clinician before using any peptide.

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Summary

ALT-801 is an investigational bifunctional fusion protein examined for two distinct therapeutic strategies: as a dual agonist of the glucagon‑like peptide‑1 (GLP‑1) and glucagon receptors to treat metabolic liver disease, and as an interleukin‑2 (IL‑2) fused to a soluble T‑cell receptor that targets the p53 peptide/HLA‑A*0201 complex on cancer cells. Preclinical mouse work shows metabolic and histologic benefits in non‑alcoholic steatohepatitis (NASH), while a phase‑I oncology trial evaluated safety and immune activation in patients with advanced malignancies.

Mechanism of Action

In the metabolic indication, ALT‑801 binds and activates both GLP‑1 and glucagon receptors, stimulating appetite suppression, weight loss, hepatic fatty‑acid oxidation and reduced lipogenesis, which together improve liver steatosis and inflammation. In the oncology setting, the molecule consists of IL‑2 covalently linked to a single‑chain T‑cell receptor domain that specifically recognizes the p53‑derived peptide (aa264‑272) presented by HLA‑A*0201 on tumor cells, delivering IL‑2‑mediated proliferative and activation signals to immune cells directed at the cancer target.

What the Research Shows

A 2022 pre‑clinical study in diet‑induced obese mice with biopsy‑confirmed NASH showed that daily ALT‑801 treatment for 12 weeks produced ~25% body‑weight loss, lowered plasma aminotransferases, cholesterol and liver triglycerides, and markedly reduced histologic steatosis, inflammation (galectin‑3) and fibrosis (collagen‑type‑I) compared with semaglutide, elafibranor or vehicle. Separately, a phase‑I trial in 26 patients with p53+/HLA‑A*0201 advanced cancers administered ALT‑801 intravenously (four daily 15‑minute infusions, repeated after a 10‑day rest). The maximum tolerated dose was 0.04 mg/kg; dose‑limiting toxicities included transient thrombocytopenia and a myocardial infarction. Pharmacokinetics showed a 4‑hour half‑life, and treatment induced serum IFN‑γ without TNF‑α elevation. Clinically, ten patients achieved stable disease for ≥11 weeks, and one melanoma patient remained disease‑free after lesion resection.

Reported Benefits

Preclinical data suggest ALT‑801 can induce substantial weight loss and improve liver biochemistry and histology in NASH models, potentially offering a novel metabolic therapy. Early clinical experience in cancer patients indicates that the IL‑2/TCR fusion can be delivered safely at defined doses, elicits immune activation (IFN‑γ rise), and may produce disease stabilization in a subset of patients, pointing to possible antitumor activity.

Limitations of the Evidence

Human efficacy data for the metabolic application are absent; the NASH findings are limited to a single mouse model. The oncology evidence is confined to a phase‑I trial with a small cohort, focusing on safety rather than definitive efficacy, and the observed responses were limited to stable disease. The dual mechanistic descriptions reflect distinct product versions, and no direct comparative studies exist. ALT‑801 remains investigational with no regulatory approval for any indication.

Safety Considerations

In the oncology trial, the most serious adverse events were a grade 4 transient thrombocytopenia and a myocardial infarction, which defined the maximum tolerated dose of 0.04 mg/kg. Other toxicities resembled those of high‑dose IL‑2, including flu‑like symptoms, hypotension and capillary leak, but were generally of lower severity. Preclinical NASH studies did not report safety concerns, but translation to humans remains untested. Careful monitoring for cardiovascular and hematologic events is warranted in future trials.

How It Is Administered

ALT‑801 has been administered intravenously as a short (≈15 minute) infusion in clinical oncology studies, with dosing cycles of four consecutive daily infusions followed by a rest period. The investigational formulation is a recombinant fusion protein; subcutaneous administration has been listed as a possible route but has not been described in published trials.

Routes of Administration

IntravenousSubcutaneous

Goals & Uses

  • NK/T cell activationImmunostimulationModerate
  • Melanoma treatmentOncologyLow
  • Targeted IL-2 deliveryPharmacologyModerate
  • Anti-tumor immunotherapyOncologyModerate
  • Cancer immunotherapyOncologyModerate
  • Bladder cancer treatmentOncologyModerate

Contraindications

  • Organ transplantationTransplantHigh
  • Severe cardiopulmonary dysfunctionCardiovascular/PulmonaryHigh
  • Severe autoimmune diseaseImmunologicalHigh
  • HLA-A*0201 negative statusGenetic/HLA RestrictionHigh
  • Active organ transplantation/immunosuppressionImmunologicalModerate

Adverse Effects

  • Cytokine release syndromeImmunologicCommonSystemic inflammatory response from immune activation
  • Lymphocytosis / eosinophiliaHematologicalCommon
  • Capillary leak syndromeVascularUncommonLeakage of fluid from blood vessels into tissues
  • Flu-like symptoms (fever, chills, fatigue)ConstitutionalCommon
  • HypotensionCardiovascularUncommonLow blood pressure
  • Nausea/vomitingGastrointestinalCommon
  • Injection site / infusion reactionsLocal/SystemicCommon
  • Vascular leak syndromeCardiovascularUncommon
  • Elevated liver enzymesHepaticUncommonIncrease in AST/ALT or other hepatic markers

Drug Interactions

  • Antihypertensive agentsModerate
  • CyclosporineModerate
  • CorticosteroidsModerate
  • Other immunosuppressantsModerate

Population Constraints

  • Severe renal or hepatic impairmentOrgan FunctionRelative
  • HLA-A*0201 negative patientsGeneticAbsolute
  • Pediatric patientsAgeRelative
  • Pregnant or breastfeeding womenReproductiveRelative
  • Pregnant womenReproductiveAbsolute

Regulatory Status

  • European UnionInvestigationalClinical development under EMA oversight.
  • United StatesInvestigationalPhase II trials ongoing; not FDA‑approved.
  • United KingdomUnknownNo MHRA approval on record; investigational status.

ALT-801 has been studied in Phase I/II clinical trials. It has received investigational new drug (IND) status in the US but has not received FDA or EMA approval. Development was led by Altor BioScience.

Evidence & Sources

Frequently Asked Questions

What is ALT‑801?

ALT‑801 is an experimental fusion protein that either acts as a dual GLP‑1/glucagon receptor agonist for metabolic liver disease or as an IL‑2 linked to a T‑cell receptor that targets a p53 peptide on cancer cells, depending on the study.

How does ALT‑801 work in cancer patients?

The drug combines interleukin‑2 with a soluble T‑cell receptor that binds the p53 peptide presented by HLA‑A*0201 on tumor cells, delivering IL‑2 signals that activate immune cells specifically against those cancer cells.

Has ALT‑801 been shown to cure any disease?

No. In mice, ALT‑801 improved liver pathology associated with NASH, and in a phase‑I cancer trial it was safe at certain doses and produced disease stabilization in some patients, but definitive cure or efficacy has not been demonstrated.

What side effects have been observed?

The oncology trial reported dose‑limiting toxicities of transient severe thrombocytopenia and a myocardial infarction, along with milder IL‑2‑type effects such as flu‑like symptoms, hypotension and capillary leak. Preclinical metabolic studies did not report adverse events.

Is ALT‑801 approved for clinical use?

No. ALT‑801 remains an investigational agent with no regulatory approval for any indication; it is currently being studied in early‑phase clinical trials.

What is ALT-801 used for?

ALT-801 is educationally associated with: NK/T cell activation, Melanoma treatment, Targeted IL-2 delivery, Anti-tumor immunotherapy, Cancer immunotherapy, Bladder cancer treatment. Educational only — not medical advice.

How is ALT-801 administered?

Recorded routes of administration: Intravenous, Subcutaneous.

What are the potential side effects of ALT-801?

Reported adverse effects include: Cytokine release syndrome, Lymphocytosis / eosinophilia, Capillary leak syndrome, Flu-like symptoms (fever, chills, fatigue), Hypotension, Nausea/vomiting, Injection site / infusion reactions, Vascular leak syndrome, Elevated liver enzymes. This list is not exhaustive — consult a qualified clinician.

Who should avoid ALT-801?

Recorded contraindications: Organ transplantation, Severe cardiopulmonary dysfunction, Severe autoimmune disease, HLA-A*0201 negative status, Active organ transplantation/immunosuppression. Consult a qualified clinician before use.

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