We offer a one-stop service from molecular design (mutein, linker, TAA selection) to comprehensive pre-clinical PK/PD validation, drastically accelerating your pre-clinical development pathway.
Creative Biolabs' tumor-targeted IL-15 delivery engineering services are designed to overcome the core limitations of systemic cytokine delivery-namely, toxicity and short half-life focusing on precision molecular design. We provide comprehensive, customized engineering of IL-15 candidates, including super-agonists and pro-cytokine systems, fused to your chosen targeting moiety. Clients gain access to validated, high-quality IL-15 fusion proteins with superior tumor localization and a drastically improved therapeutic window, significantly accelerating their research programs toward advanced pre-clinical development.
Interleukin-15 (IL-15) is a T cell and NK cell growth factor with proven anti-tumor activity, signaling through the IL-2Rβ/IL-2Rγ chains. However, its short native half-life and off-target activation cause systemic toxicity. Creative Biolabs' tumor-targeted IL-15 delivery engineering services solve this by creating Immunocytokines and procytokines that are inert until activated in the tumor microenvironment (TME). IL-15 secreted by the tumor itself is an essential prerequisite for cytotoxic innate lymphoid cells (ILC1s) to mount effective immunosurveillance, strongly validating the need for high local concentrations achievable only through precision targeting.
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Fig.1 Schematic representation describing the tumor-targeted biNV-IL-15. 1
We offer a one-stop service from molecular design (mutein, linker, TAA selection) to comprehensive pre-clinical PK/PD validation, drastically accelerating your pre-clinical development pathway.
Implementation of our advanced pro-cytokine systems with TME-selective protease-cleavable linkers guarantees that the active cytokine is only released in situ and achieves superior systemic safety.
All constructs are designed using quality-by-design (QbD) principles, ensuring optimized codon usage, stable expression in industrial microbial/mammalian systems, and seamless transfer for future large-scale manufacturing.
Rigorous assessment and documentation of strain/cell line origin, ensuring the stability of candidates in cell banks and during large-scale production, backed by high-standard quality control tools.
This modality focuses on the rational design and synthesis of next-generation multispecific constructs. These sophisticated platforms integrate the IL-15 super-agonist with multiple binding domains, thereby creating potent immune engagers that localize IL-15 activity while simultaneously bridging tumor cells with NK or T cells.
This service is dedicated to creating stabilized IL-15 fusion proteins utilizing a conventional IgG or Fc-based scaffold. This design leverages the proven half-life extension and stability inherent to the IgG format while directing the potent IL-15 payload via high-affinity TAA binding for precise delivery to the tumor microenvironment.
We mitigate the severe injection site reactions and systemic AEs seen with non-targeted half-life extenders like hetIL-15 by ensuring the cytokine is only active or released within the tumor microenvironment, leading to a drastically improved safety margin.
Our proprietary functional assays explicitly test for the expansion and cytotoxic capacity of innate lymphoid cells, which recent research confirms are critical effectors of tumor immunosurveillance and are stimulated by IL-15.
We offer conditional activation systems that eliminate systemic activity, ensuring that the circulating drug is inert until activated by a TME-specific cue (e.g., low pH or MMP cleavage), offering the highest therapeutic control.
Based on published data comparing IL-15 to IL-2, our approach leverages the six times lower toxicity of IL-15 while eliminating off-target activity, achieving an optimal 3-fold higher therapeutic index compared to native IL-2 programs.
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A: Non-targeted fusions like ALT-803 extend half-life but are associated with severe systemic side effects, including injection site reactions, which limit dosing. Our targeted approach ensures the same high potency and half-life extension but confines activity to the tumor, vastly improving the therapeutic window and safety profile.
A: We specialize in integrating IL-15 fusions with a wide range of TAA antibodies, including those targeting TME-specific "silent" antigens like the EDB domain of fibronectin. We offer consultation to select the optimal target based on your specific tumor indication to ensure maximal localization and minimal off-target binding.
Comprehensive in silico and in vivo analysis services to accurately predict the therapeutic window and optimal dosing schedule of your targeted therapeutic.
Learn More →Identification, sequencing, and affinity maturation of high-affinity TCRs specific for your target MHC-peptide complex, providing the foundational targeting moiety for TCR-IL-15 fusion development.
Learn More →Creative Biolabs ensures that the potent immune-stimulatory effects of IL-15 are localized to the tumor, driving superior efficacy while dramatically improving research safety. Our expert team is prepared to discuss your specific TAA, therapeutic goals, and timeline. Please contact us.
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