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  • [ Recombinant Protein ] A facilitator: IL-4 improves the application of B lymphocytes in clinical.

[ Recombinant Protein ] A facilitator: IL-4 improves the application of B lymphocytes in clinical.

2023-02-06
How does the IL-4 signaling work?

The IL-4 receptor alpha chain (IL-4R) mediates the action of IL-4 signaling. After ligand binding, the IL-4R dimerized either with the common gamma chain (γc) to generate the type-1 signaling complex, which is mostly seen on hematopoietic cells and specifically binds IL-4, or with the IL-13 receptor alpha 1 (IL-13Rα1) to generate the type-2 complex, which is also present on non-hematopoietic cells. The type-1 signaling complex is essential for the Th2-skewing of T cells and the growth of alternatively activated macrophages (AAMs), whereas the type-2 complex is involved in non-hematopoietic responses to IL-4 and IL-13, such as airway hyperreactivity and mucus formation. Both complexes activate JAKs and STAT6 in the downstream pathway. [1, 2] The type-1 signaling complex can also activate the downstream pathway via PI3K/Akt, which is relied on the common gamma chain (γc) transmission.
 


 
How does IL-4 be used in cell therapy?

As above mentioned, the IL-4 signaling pathway is important to various cell differentiation, Immunoglobulin generation, and other functions. In fact, research shows that the IL-4/STAT6 signaling pathway is highly related to tumor development by gaining apoptosis resistance and evading immune surveillance. [3] However, there are other mechanisms that imply IL-4 has the potential to be a therapeutic target via enhancing and diverting T and B cell activities.

 
♦ B Cell-Based Cancer Immunotherapy

Patients who have undergone allogeneic stem cell transplantation (alloSCT) have both a T- and a B-lymphocyte-related immunological deficit that lasts for a long time. Normally, it takes 1-2 years to recover which is defined by functional B-cell immunity. So, the researchers came up with an idea, to enhance B-cell immune reconstitution after alloSCT, they started to work on the adoptive transfer of memory B-cells from the original stem cell donor. [4] Generally, soluble CD40L and IL-4 are added to human peripheral blood mononuclear cells (PBMCs) or purified B cells during a minimum of 14 days of culture [5], with the addition of IL-4 being critical for B-cell proliferation. [6, 7] Several studies have shown that the B cell culture conditions described above lead to about 20 times higher expansion ability and possess an antigen-presenting function. [8]




Related Products:
→ Croyez GMP ® IL-4 (Interleukin-4), Human
→ IL-4 (Interleukin-4), Human
→ IL-13 (Interleukin-13), Human
 
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  1. Chomarat P, Banchereau J. An update on interleukin-4 and its receptor. Eur Cytokine Netw. 1997 Dec;8(4):333-44.
  2. Delgado-Ramirez Y, Colly V, Gonzalez GV, Leon-Cabrera S. Signal transducer and activator of transcription 6 as a target in colon cancer therapy. Oncol Lett. 2020 Jul;20(1):455-464.
  3. Zhang WJ, Li BH, Yang XZ, Li PD, Yuan Q, Liu XH, Xu SB, Zhang Y, Yuan J, Gerhard GS, Masker KK, Dong C, Koltun WA, Chorney MJ. IL-4-induced Stat6 activities affect apoptosis and gene expression in breast cancer cells. Cytokine. 2008 Apr;42(1):39-47.
  4. Julia Winkler, MD, Hannes Tittlbach, Wolf Roesler, MD, Julian Strobel, MD, Roland Zimmermann, MD, Stefanie Maas, MD, Bernd Spriewald, MD, Daniel Wolff, MD, Roland Repp, MD, Lambros Kordelas, MD, Michael Mach, PhD, Andreas Mackensen, MD, Thomas H. Winkler, PhD. Adoptive Transfer of Purified Donor-B-Lymphocytes after Allogeneic Stem Cell Transplantation: Results from a Phase I/IIa Clinical Trial. Blood (2016) 128 (22): 502.
  5. Garcia-Marquez MA, Shimabukuro-Vornhagen A, Theurich S, Kochanek M, Weber T, Wennhold K, Dauben A, Dzionek A, Reinhard C, von Bergwelt-Baildon M. A multimerized form of recombinant human CD40 ligand supports long-term activation and proliferation of B cells. Cytotherapy. 2014 Nov;16(11):1537-1544.
  6. Tadmori W, Lee HK, Clark SC, Choi YS. Human B cell proliferation in response to IL-4 is associated with enhanced production of B cell-derived growth factors. J Immunol. 1989 Feb 1;142(3):826-32.
  7. Wennhold K, Shimabukuro-Vornhagen A, von Bergwelt-Baildon M. B Cell-Based Cancer Immunotherapy. Transfus Med Hemother. 2019 Feb;46(1):36-46.
  8. von Bergwelt-Baildon MS, Vonderheide RH, Maecker B, Hirano N, Anderson KS, Butler MO, Xia Z, Zeng WY, Wucherpfennig KW, Nadler LM, Schultze JL. Human primary and memory cytotoxic T lymphocyte responses are efficiently induced by means of CD40-activated B cells as antigen-presenting cells: potential for clinical application. Blood. 2002 May 1;99(9):3319-25.
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