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Research topics

Immunomodulatory peptides

Treating the immune system as a network rather than a single target, and packing several modulations into one peptide — Immunokine.

What this research is trying to do

Immune therapeutics have long been built around a single target. But the immune system is a densely interconnected network: block one node and another compensates, while feedback loops reassert themselves. That is usually where the effect of a monospecific agent dulls and resistance appears.

The Immunokine is an engineered peptide that consolidates receptor-biased cytokine signalling and multi-target checkpoint modulation within one molecule. What separates it from combining antibodies is that it is designed rather than assembled — structure-first computational engineering, multivalent scaffolds, and chemistry that reconciles potency with tolerability.

What recurs across diseases

Read across oncology, autoimmunity, inflammation, neurology, metabolism and infection, the mechanisms converge on a few: simultaneous checkpoint and costimulatory modulation, coupled cytokine and innate signalling control, and macrophage repolarization — the last appearing as a therapeutic node in diseases as far apart as tumour immunity and fungal keratitis.

The preclinical evidence lines up the same way: cereblon-dependent molecular glue degraders achieving nanomolar multi-neosubstrate degradation and complete tumour regression; epitope-directed vaccines that preserve stress ligand display; and pleiotropic neuropeptides and secretomes that rebalance neuroinflammation.

Where to put it

Immune modulation is activity that must not switch on just anywhere, which makes delivery and stabilization design variables as consequential as potency. Nanocarriers, self-assembling hydrogels, microneedles and engineered vesicles all exist to confine activity in space and time.

What contextBio does

Designing the binder from structure uses the same tools as generative binder design and peptide drugs — PepDesigner is that place. The difference is the evaluation criterion: judgement rests on the network-level response, not binding free energy, which puts this work next to virtual cell research.

What remains

Standardization and safety are the open gates. One molecule touching several nodes means the wanted and unwanted effects come from the same principle. Whether this matures into a scalable therapeutic class depends on drawing that boundary with data.

References

20 items

This page draws on the review manuscript Immunokine: Design and Development of Multi-Target Immunomodulatory Peptide Therapeutics; below is the literature it cites.

  1. Islam MK, Stanslas J. Peptide-based and small molecule PD-1 and PD-L1 pharmacological modulators in the treatment of cancer. Pharmacol Ther. 2021;227:107870. doi:10.1016/j.pharmthera.2021.107870
  2. Upadhyay S, Kaur B, Gabr MT. CD28 and ICOS in immune regulation: structural insights and therapeutic targeting. Bioorg Med Chem Lett. 2025;123:130310. doi:10.1016/j.bmcl.2025.130310
  3. Lin J, Zhang X, Cheng A, Ren M, Yao X, Sun X, et al. Delivery of peptide-LYTAC via polyporus polysaccharide microneedles for targeted CD47 degradation and enhanced tumor immunotherapy. J Am Chem Soc. 2025;147(27):24178-24192. doi:10.1021/jacs.5c08368
  4. Song S, Xu H, Liu M, Xu Q, Wang L, Wang F, et al. Isoimperatorin alleviates fungal keratitis by regulating NF-kappaB pathway and macrophage immune response. Front Immunol. 2026;17:1676397. doi:10.3389/fimmu.2026.1676397
  5. Li P, Hu X, Fan Z, Sun S, Ran Q, Wei T, et al. Novel potent molecular glue degraders against broad range of hematological cancer cell lines via multiple neosubstrates degradation. J Hematol Oncol. 2024;17(1):77. doi:10.1186/s13045-024-01592-z
  6. Wang R, Wu J, Lin Y, Xiao Y, Yang B, Yao S, et al. An epitope-directed mRNA vaccine inhibits tumor metastasis through the blockade of MICA/B alpha1/2 shedding. Cell Rep Med. 2025;6(3):101981. doi:10.1016/j.xcrm.2025.101981
  7. Castillo-Gonzalez J, Buscemi L, Vargas-Rodriguez P, Serrano-Martinez I, Forte-Lago I, Caro M, et al. Cortistatin exerts an immunomodulatory and neuroprotective role in a preclinical model of ischemic stroke. Pharmacol Res. 2024;210:107501. doi:10.1016/j.phrs.2024.107501
  8. Amodeo G, Niada S, Galimberti G, Franchi S, Della Morte E, Taiana M, et al. Insights into mesenchymal stem/stromal cell conditioned media as a long-lasting treatment for pain and psychiatric comorbidities in a murine model of osteoarthritis. Brain Behav Immun. 2026;127:106297. doi:10.1016/j.bbi.2026.106297
  9. Xiong Y, Cai H, Jia S, Gong B, Hou K, Wu H, et al. Nanocarrier-enabled melittin therapy: mechanistic advances, therapeutic applications, and translational challenges. Int J Nanomedicine. 2026;21:1-24. doi:10.2147/IJN.S599827
  10. Falcone N, Ermis M, Tamay DG, Mecwan M, Monirizad M, Mathes TG, et al. Peptide hydrogels as immunomaterials and their use in cancer immunotherapy delivery. Adv Healthc Mater. 2023;12(27):e2301096. doi:10.1002/adhm.202301096
  11. Klebanoff CA, Chandran SS, Baker BM, Quezada SA, Ribas A. T cell receptor therapeutics: immunological targeting of the intracellular cancer proteome. Nat Rev Drug Discov. 2023;22(12):996-1017. doi:10.1038/s41573-023-00809-z
  12. Zhen Q, Wang Y, Li Z, Sun L. Advances in genetic-immunological targeted therapies for psoriasis. Curr Opin Immunol. 2025;94:102559. doi:10.1016/j.coi.2025.102559
  13. Hemmati S, Rasekhi Kazerooni H. Polypharmacological cell-penetrating peptides from venomous marine animals based on immunomodulating, antimicrobial, and anticancer properties. Mar Drugs. 2022;20(12):763. doi:10.3390/md20120763
  14. Nordin ML, Azemi AK, Nordin AH, Nabgan W, Ng PY, Yusoff K, et al. Peptide-based vaccine against breast cancer: recent advances and prospects. Pharmaceuticals (Basel). 2023;16(7):923. doi:10.3390/ph16070923
  15. Suryaningtyas IT, Jung WK, Lee SJ, Je JY. Bioactive peptides PIISVYWK and FSVVPSPK improve glucose homeostasis by targeting DPP-IV and glucose transport in type 2 diabetic mice. Int Immunopharmacol. 2025;158:114844. doi:10.1016/j.intimp.2025.114844
  16. Mishra V, Agrawal S, Malik D, Mishra D, Bhavya B, Pathak E, et al. Targeting matrix metalloproteinase-1, matrix metalloproteinase-7, and serine protease inhibitor E1: implications in preserving lung vascular endothelial integrity and immune modulation in COVID-19. Int J Biol Macromol. 2025;308:141602. doi:10.1016/j.ijbiomac.2025.141602
  17. Pei W, Zhang Y, Zhu X, Zhao C, Li X, Lu H, et al. Multitargeted immunomodulatory therapy for viral myocarditis by engineered extracellular vesicles. ACS Nano. 2024;18(6):4863-4885. doi:10.1021/acsnano.3c05847
  18. Li S, Wang H. Peptide hydrogels for postoperative tumor therapy: enhancing immune modulation and local drug delivery. WIREs Nanomed Nanobiotechnol. 2025;17(6):e70043. doi:10.1002/wnan.70043
  19. Jariene V, Valiukevicius P, Insodaite R, Janonyte U, Maciulaitis R, Maciulaitis J, et al. In vitro and ex vivo immunomodulatory effects of human placental mesenchymal stem cells in hidradenitis suppurativa. Front Immunol. 2025;16:1642014. doi:10.3389/fimmu.2025.1642014
  20. Sha S, Sun C, Gao X, Bi W, Chen H, Ren W, et al. Engineered stem cell membrane-coated nanodrugs for targeted therapy of Alzheimer's disease. ACS Appl Mater Interfaces. 2025;17(32):45210-45226. doi:10.1021/acsami.5c09843

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