ArticleJournal for immunotherapy of cancer2025
Selective activation of interleukin-2/interleukin-15 receptor signaling in tumor microenvironment using paired bispecific antibodies.
Article in Journal for immunotherapy of cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- αTIGIT-guided IL-15 mimetics drive potent and safe antitumor immunity by restoring tumor-infiltrating T cells.Cellular & molecular immunology · 2026Article
- Therapeutic Resistance in Melanoma: Molecular Mechanisms and Emerging Pharmaceutical Strategies.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Microenvironment plays a critical role in modulating tumor cell dormancy: Current perspectives and potential treatment options.World journal of clinical oncology · 2026Review
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Authors and funding
14 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundOwing to their roles in promoting T cell and natural killer (NK) cell activation and proliferation, interleukins-2 (IL-2) and interleukins-15 (IL-15) have been pursued as promising pathways to target in cancer immunotherapy. Nonetheless, their wider therapeutic application has been hampered by severe dose-limiting toxicities including systemic cytokine release and organ edema for IL-2, and inconvenient intratumoral administration for IL-15. To address these safety issues, we generated IL-2R/IL-15R×TAA (tumor-associated antigen) bispecific antibody (bsAb) pairs to selectively activate IL-2R signaling in the tumor microenvironment.
methodsEach bsAb pair is composed of one bsAb targeting CD122 and a TAA epitope, and the other bsAb targeting CD132 and the same or a different TAA epitope. In vitro assays were performed to characterize the IL-2R/IL-15R agonistic activity of the bsAb pairs, as well as their capacity to enhance T-cell-mediated killing of TAA
resultsWe demonstrated with two different TAAs (human epidermal growth factor receptor 2 (HER2) and mesothelin (MSLN)) that the CD122×TAA/CD132×TAA bsAb pairs mediate effective activation of immune cells exclusively in the presence of TAA
conclusionsOverall, the findings suggest that this innovative therapeutic approach effectively leverages the antitumor activity of IL-2 and IL-15 pathways while minimizing their associated systemic toxicities. This dual bsAb format holds potential for broader application in other immune-activating pathways.
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