Immunostimulatory Cytokine-based Cancer Immunotherapy

Cytokines such as interleukins and interferons play a role in regulating physiological functions, including immunity, development, growth, and tissue repair. Recent studies have shown that the mechanism of cytokine receptor activation has been provided with new approaches and insights through the combination of structural biology, protein engineering, and receptor pharmacology, while also suggesting that the function of cytokines is highly tunable. Creative Biolabs provides a variety of immunostimulatory cytokine design strategies to safely and effectively modulate cytokine activity for therapeutic purposes.

Fig.1 Molecular Engineering Strategies for Cytokine Optimization.¹

Our Service

Some intrinsic properties of cytokines greatly hinder their therapeutic effects, e.g., shorter half-lives, off-target effects, and functional polymorphisms. Creative Biolabs provides immunostimulatory cytokine-based cancer immunotherapy development services to enhance the therapeutic potential of cytokines through a variety of approaches and strategies, including modifying binding domains, extending half-lives, and forming fusion proteins and bifunctional cytokines.

• The use of natural cytokines may be limited by factors such as short half-lives and toxicity in vivo. Extended half-life can be achieved through a variety of pathways, including fusion with other proteins (e.g., immunoglobulin, its Fc region, or albumin).
  

  What We Can Offer	Methods
  Prolongs cytokine half-life	Protein fusion, PEGylation

  
  
  • Published Data

Fig.2 Modified IL-2 for cell targeting and extended half-life.²

• In addition to linkage to albumin or PEGylation, other engineering methods to influence cytokine delivery have been developed. These include: polymeric matrix, which can be implanted in an ideal location near the tumor; microparticles (>1 μm), such as polymer microparticles, including lipid or solid polymer microparticles; There are also nanoparticles (10-100nm), which have the unique property of small size.
  

  What We Can Offer	Methods
  Optimize cytokine delivery	Polymerization matrix; Microparticles; Nanoparticles

  
  
  • Published Data

Fig.3 In vivo properties of GM-CSF-IL-7 fusion cytokines.³

• Another way to prolong the half-life of cytokines, as well as potentially influence their receptor interactions, is the formation of cytokine-anti-cytokine complexes or immune complexes.

• Engineered cytokine receptors or cytokine-receptors pairs have also been used to enhance cytokine activity.

• The production of cytokine mutants is a method that has been used for many years to create molecules with altering activity, where mutations can potentially increase or decrease the affinity of cytokines. For cytokines involved in more than one cytokine receptor chain, interactions with each chain can be selectively localized, with potentially different effects.
  

  What We Can Offer	Methods
  Cytokine mutant	IL-2Rα or IL-2Rβ mutations; IL-2 super-agonists and partial agonists;

  
  
  • Published Data

Fig.4 Effect of IL2RB-encoding mutations on IL-2Rb surface receptors.⁴

• In addition to native cytokines, soluble cytokine-cytokine receptor complexes or fusion proteins may also be used, depending on the nature of the cytokine receptor.

• Others

Prospect and Future

Creative Biolabs scientists have been working on a variety of different modification strategies to tune cytokine functional activity and have developed mechanism-based protein engineering strategies that are able to systematically modulate cytokine receptor activity.

The immunostimulatory cytokine-based cancer immunotherapy development services we offer go beyond the strategies listed above. You can also get in touch with us directly to get a solution about your research goals or exact protocol. Based on advanced technology and rich experience in immunotherapy, we will provide you with satisfactory methods and results!

References

1. Vazquez-Lombardi.; et al. "Molecular Engineering of Therapeutic Cytokines" Antibodies. (2013). 2, no. 3: 426-451.
2. Raker, V.K.; et al. "Targeted activation of T cells with IL-2-coupled nanoparticles." Cells. (2020). 9,9 2063.
3. Shireman, J.M.; et al. "GM-CSF and IL-7 fusion cytokine engineered tumor vaccine generates long-term Th-17 memory cells and increases overall survival in aged syngeneic mouse models of glioblastoma." Aging cell. 22,7 (2023): e13864.
4. Zhang, Zinan.; et al. "Human interleukin-2 receptor β mutations associated with defects in immunity and peripheral tolerance." The Journal of experimental medicine. 216,6 (2019): 1311-1327.

For Research Use Only | Not For Clinical Use