Advancing Immunotherapy Development with High-Quality Cytokines

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An illustration of common cytokine targets in cancer research.

Because abnormal cytokine levels in the tumor microenvironment drive cancer pathogenesis, scientists are currently generating therapies targeting these proteins.

Cytokines are small, secreted proteins that transmit messages between cells and members of this superfamily include chemokines, growth factors, interleukins, interferons, colony stimulating factors, and tumor necrosis factors (TNF).1 Produced by many cell types including immune cells, these molecules can act on the cells that generate them or nearby cells. Upon binding to their surface receptors, cytokines trigger downstream signaling cascades associated with many cellular processes, such as differentiation, tissue repair, proliferation, migration, and immune responses.1 Because these proteins affect diverse pathways, researchers have investigated their involvement in many diseases including cancer, inflammatory disorders, and autoimmune diseases and established that cytokine dysregulation contributes to their pathogenesis. 

Cancer Drug Targets or Potential Therapies?

Scientists determined that overexpression of some cytokines or their receptors, such as TNF, interleukin-6 (IL-6), IL-6 receptor, interleukin-1β (IL-1β), and interleukin-1 receptor, in cancer cells promotes their excessive proliferation, expansion, and resistance to therapies.1 Additionally, the malignant cells’ increased cytokine secretion recruits stromal and immunosuppressive cells to the tumor site, resulting in elevated extracellular matrix production, new blood vessel generation, and immune evasion. This allows the cancer cells to generate their ideal tumor microenvironment (TME) that supports their growth while limiting antitumor immune activity. 

To overcome cytokine dysregulation in cancer, researchers devised several strategies to neutralize protumor cytokine activities and induce protective antitumor immune responses. Scientists have designed antagonists, such as monoclonal antibodies, small molecule inhibitors, and cytokine traps, to impede cancer progression by binding directly to cytokines or their receptors and blocking the activation of specific signaling pathways.2 For instance, mogamulizumab, the monoclonal antibody against CC chemokine receptor 4, is showing promising results in patients with a variety of cancers including adult T-cell leukemia-lymphoma, lung cancer, and cutaneous T-cell lymphoma.3 

     An illustration of cells growing in the presence of cytokines.

Researchers rely on recombinant cytokines for immune cell culture and immunotherapy generation.

Sino Biological

Alternatively, they have employed cytokines directly as therapies including interferon-α (IFN-α) and interleukin-2 (IL-2). By administering recombinant cytokines intravenously, clinicians increase their levels in the TME to promote cancer cell apoptosis or immune stimulation. However, cytokines have short circulatory half-lives and can affect both malignant and normal cells leading to off-target effects and toxicity.4 Researchers are now investigating new methods to improve their delivery to the tumor, such as fusing cytokines to antibodies or other proteins, designing nanoparticles to carry the molecules, or employing tumor-homing mesenchymal stem cells expressing the therapeutic cytokines. Moreover, clinicians have started using cytokine or cytokine antagonists alongside existing cancer therapies to improve their efficacy and diminish their adverse effects.1

Besides cytokine-based and -directed treatments, scientists also employ these proteins to produce cellular therapies. Researchers use cytokines, such as IL-2, interleukin-7 (IL-7), interleukin-15 (IL-15), and interleukin-21 (IL-21) for culturing immune cells for cancer immunotherapies including chimeric antigen receptor (CAR) T cell or tumor infiltrating lymphocyte (TIL) therapies.1

Choosing High-Quality Cytokines for Research and Clinical Applications 

Safe and high-quality cytokines are critical for both scientists investigating the importance of particular cytokines to cancer pathogenesis and antitumor immune activity and those developing immunotherapies or anticytokine therapies for cancer treatment. With over 800 cytokine products, Sino Biological offers a comprehensive range of recombinant cytokines, such as IFN-α, IL-1β, IL-2, IL-6, IL-7, IL-15, IL-21, and TNF, from a variety of species including human, mouse, rat, and more. The rigorous quality control process the company uses to assess purity, endotoxin levels, sterility, and mycoplasma presence ensures their research-grade products display high purity, bioactivity, stability, and consistency between batches. This allows researchers to obtain trustworthy research results. Additionally, Sino Biological offers even higher quality and stable recombinant cytokines, which they produce following good manufacturing practice (GMP) standards. Because of this strict manufacturing process, these GMP-grade cytokines have excellent safety profiles which makes them ideal for cell therapy development, such as TIL and CAR T therapies.

References

  1. Propper DJ, Balkwill FR. Harnessing cytokines and chemokines for cancer therapy. Nat Rev Clin Oncol. 2022;19(4):237-253.
  2. Berraondo P, et al. Cytokines in clinical cancer immunotherapy. Br J Cancer. 2019;120(1):6-15.
  3. Zhang T, et al. Safety and efficacy profile of mogamulizumab (Poteligeo) in the treatment of cancers: An update evidence from 14 studies. BMC Cancer. 2021;21(1):618.
  4.  Deckers J, et al. Engineering cytokine therapeutics. Nat Rev Bioeng. 2023;1(4):286-303.
     Sino Biological
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