Immune Cell Therapy (CAR-T/NK)

4-1BB, also known as CD137, belongs to the same tumor necrosis factor (TNF) receptor family as OX40. 4-1BB is encoded by the tumor necrosis factor receptor superfamily member 9 (TNFRSF9) gene. As an inducible co-stimulatory receptor, 4-1BB is expressed on the activated CD4+ and CD8+ T cells, as well as NKT, NK, DC, and Tregs cells. Anti-4-1BB antibodies can: 1) activate the co-stimulatory signals of 4-1BB and stimulate the expansion of CD4+ effector T cells to produce pro-inflammatory cytokines; 2) stimulate the proliferation of CD8+ cytotoxic T cells to improve their effects; 3) induce DC maturation and promote antigen presentation; and 4) stimulate and enhance the ADCC effect of NK cells. Recombinant Anti-Human 4-1BB mAb is expressed by mammalian cells, and is produced with raw materials of pharmaceutical applicable level. The host protein residue, nucleic acid residue and common pathogens are strictly controlled, and the production and quality management procedures of the product comply with GMP regulations to ensure the traceability of the production process and all raw materials.

CD16, also known as Fc γ RIII, is an Fc fragment receptor of IgG. It is widely expressed on the surface of NK cells, neutrophil polymorphonuclear leukocytes, mononuclear cells, and macrophages, and is one of the main surface markers of NK cells. CD16 is involved in antibody-dependent cell-mediated cytotoxicity (ADCC) by binding to the Fc of IgG, which in turn activates NK cells. CD16 acts as a low-affinity receptor on the Fc of some IgG to bind to the γ chain of Fc ε-associated receptor I of CD3 ζ (εRI of Fc), thus participating in signal transduction. In addition, CD16 can increase the toxicity of NK cells, upregulate the expression of the genes such as IL-2R, IFN-gamma, and TNF-alpha, increase the secretion of corresponding factors, and serve to activate NK cells and promote proliferation in vitro. Recombinant Anti-Human CD16 mAb is expressed by mammalian cells, and is produced with raw materials of pharmaceutical applicable level. The host protein residue, nucleic acid residue and common pathogens are strictly controlled, and the production and quality management procedures of the product comply with GMP regulations to ensure the traceability of the production process and all raw materials.

CD28 molecule is present on the surface of most T cells and is considered a surface molecule unique to T cells. However, not only the first signal of the T lymphocyte receptor (TCR)/CD3 complex is required during the full activation of T lymphocytes, but also the second signal, to enhance the activation and proliferation of T lymphocytes. The synergistic stimulation molecule CD28 is present on the surface of T lymphocytes, and its interaction with its ligand B7 is one of the major pathways to provide the second signal for T lymphocyte activation. T lymphocytes will be fully activated if the second signal is provided through the synergistic stimulation of the CD28 antibody while providing the first signal using the simulation of the CD3 antibody in vitro. Recombinant Anti-Human CD28 mAb is expressed by mammalian cells, and is produced with raw materials of pharmaceutical applicable level. The host protein residue, nucleic acid residue and common pathogens are strictly controlled, and the production and quality management procedures of the product comply with GMP regulations to ensure the traceability of the production process and all raw materials.

Recombinant Anti-Human CD3 mAb is a T cell-activated antibody produced based on OKT3 through humanization modification and genetic engineering. On the premise of maintaining the activation ability of OKT3 monoclonal antibody on T cells, the product can eliminate the immunogenicity of murine antibodies to the greatest extent. The product recognizes the human TCR ε chain to activate the T cell activation signaling pathway, thus stimulating T cell activation and proliferation. Recombinant Anti-Human CD3 mAb is expressed by mammalian cells, and is produced with raw materials of pharmaceutical applicable level. The host protein residue, nucleic acid residue and common pathogens are strictly controlled, and the production and quality management procedures of the product comply with GMP regulations to ensure the traceability of the production process and all raw materials.

CD52 is a glycosylated phosphatidylinositol (GPI)-anchored cell surface protein on a variety of normal and malignant lymphoid cells and is presented in large quantities (500,000 molecules/cell). CD52 is widely distributed on hematopoietic cells (such as lymphocytes and monocytes) and the surface of certain cells in the reproductive system of males. CD52 is not expressed on the surface of hematopoietic stem/progenitor cells but is distributed at a high density on lymphocytes and many hematopoietic malignant tumor cells. The molecular crosslinking can cause a series of signaling, resulting in cytokine secretion, cell proliferation, growth inhibition and apoptosis. Recombinant Anti-Human CD52 mAb is expressed by mammalian cells, and is produced with raw materials of pharmaceutical applicable level. The host protein residue, nucleic acid residue and common pathogens are strictly controlled, and the production and quality management procedures of the product comply with GMP regulations to ensure the traceability of the production process and all raw materials.

Different grades and packaging are available.

NKG2D (Natural-killer group 2, member D) is also known as NK cell receptor D or CD314. Encoded by KLRK1 gene, NKG2D is a disulfide-bonded homodimer and can form a heterohexamer with four subunits of HCST/DAP10. NKG2D contains a cytoplasmic domain (aa 1-51), helical membrane-spanning domain (aa 52-72), and extracellular domain (aa 73-216). NKG2D is mainly expressed on the surface of NK, NKT, γ δ T, and CD8+ T cells. It acts as an activating receptor to mediate the activation of the above-mentioned immune cells for killing target cells. NKG2D is involved in immune surveillance as an activated and co-stimulatory receptor after binding to various cellular stress-induced ligands on the surface of autologous tumor cells and virus-infected cells. Also, it provides stimulated and co-stimulated innate immune responses on activated natural killer (NK) cells, resulting in their cytotoxic activity. Furthermore, through expanding T cell activation, NKG2D acts as a co-stimulatory receptor for T cell receptors (TCRs) in CD8+ T cell-mediated adaptive immune responses. Recombinant Anti-Human NKG2D mAb is expressed by mammalian cells, and is produced with raw materials of pharmaceutical applicable level. The host protein residue, nucleic acid residue and common pathogens are strictly controlled, and the production and quality management procedures of the product comply with GMP regulations to ensure the traceability of the production process and all raw materials.

GM-CSF stimulates the colony formation of neutrophils and macrophages in vitro and serves for promoting the proliferation and development of early erythroid megakaryocytes and eosinophil progenitor cells. It is one of the earliest cytokines discovered to have an effect on dendritic cells (DCs). During the culture of DC, GM-CSF can promote the differentiation of monocytes into large macrophage cells, as well as the expression of MHC class II molecules on the cell surface, thus enhancing the antigen presentation function of cells. Also, GM-CSF promotes the survival of DCs. GM-CSF can activate the immune response in a variety of tumor models. The antitumor activity of GM-CSF comes from its biological function of activating macrophages and DCs. Early studies showed that CD4+ and CD8+ T cells are involved in anti-tumor immunity activated by GM-CSF. Recent studies have shown that NKT plays an important role in the antitumor activity involving GM-CSF. Recombinant Human GM-CSF is expressed by mammalian cells, and is produced with raw materials of pharmaceutical applicable level. The host protein residue, nucleic acid residue and common pathogens are strictly controlled, and the production and quality management procedures of the product comply with GMP regulations to ensure the traceability of the production process and all raw materials.

Glypicans (GPC) are a family of heparan sulfate proteoglycans that are attached to the cell surface by a glycosylphosphatidylinositol (GPI) anchor. GPC3 is closely related to the occurrence and progression of hepatic cancer, melanoma, and ovarian clear cell carcinoma. GPC3 expression is featured by high specificity. GPC3 is highly expressed in hepatic cancer and lowly expressed in melanoma, ovarian clear cell carcinoma, yolk sac tumor, neuroblastoma, hepatoblastoma, and Wilm tumor, but not expressed in breast cancer, mesothelioma, ovarian epithelial cancer, or lung cancer. GPC3 is hardly expressed in normal human tissues, so it is expected to become one of the ideal targets for liver cancer immunotherapy. Recombinant Human GPC3 is expressed by mammalian cells, and is produced with raw materials of pharmaceutical applicable level. The host protein residue, nucleic acid residue and common pathogens are strictly controlled, and the production and quality management procedures of the product comply with GMP regulations to ensure the traceability of the production process and all raw materials.

IFN-gamma (IFNγ), a class II interferon, activates macrophages and induces the expression of MHC I, MHC II, and co-activating molecules on antigen-presenting cells (APCs). IFN-gamma also can induce changes in the expression of proteasomes, thus enhancing antigen presentation. IFN-gamma also promotes the differentiation of CD4+ T cells to Th1 and inhibits the IL-4-dependent switching of B cell isotypes. IFN-gamma activates the JAK-STAT cellular pathway by phosphorylating JAK1 and JAK2 proteins. The immunomodulatory effect of interferon is manifested in its effects on the activity of host immune cells, such as macrophages, T cells, B cells, and NK cells. (1) IFN-gamma can increase the expression of MHC class II molecules on the surface of macrophages and enhance their antigen presentation ability; it also can upregulate macrophage Fc receptors to promote macrophage phagocytosis of immune complexes, antibody-coated pathogens, and tumor cells. (2) IFN-gamma promotes the differentiation of B cells and CD8+ T cells, rather than their proliferation. It can enhance the activity of TH1 cells, thus improving their cellular immune function. (3) IFN-gamma also has wide effects on other cells, including i) stimulating neutrophils and enhancing their phagocytosis; ii) activating NK cells and enhancing their cytotoxicity; and iii) stimulating the expression of MHC class II molecules on the cells where MHC class II molecules are not normally expressed (such as vascular endothelial cells, some epithelial cells and connective tissue cells), thus playing the role of antigen presentation. Recombinant Human IFN-gamma is expressed by mammalian cells, and is produced with raw materials of pharmaceutical applicable level. The host protein residue, nucleic acid residue and common pathogens are strictly controlled, and the production and quality management procedures of the product comply with GMP regulations to ensure the traceability of the production process and all raw materials.

IL-1 alpha, also known as IL-1F1, upregulates the expression of IL-2R on the surface of peripheral blood lymphocytes. When IL-1 alpha is used in combination with IFN-gamma and CD3 monoclonal antibody, the cytotoxicity of CIK can be significantly increased. IL-1 alpha stimulates the proliferation of CD4+ T cells in vitro, induces the production of IL-2, co-stimulates CD8+/IL1R+ T cell activation, and stimulates mature B cell proliferation and immunoglobulin secretion. Recombinant Human IL-1 alpha is expressed by E. coli, and is produced with raw materials of pharmaceutical applicable level. The host protein residue, nucleic acid residue and common pathogens are strictly controlled, and the production and quality management procedures of the product comply with GMP regulations to ensure the traceability of the production process and all raw materials.

IL-1beta can activate T cells to generate cytokines such as IL-2, IL-4 and IFN -γ, induce the expression of IL-2 receptor and promote T cell proliferation and differentiation. IL-1beta can synergize with IL-2 and IFN-γ to induce cytotoxic activity of NK cells and CTL.Capable of affiliating with IL-4 and other cytokines, IL-1beta can stimulate B cell proliferation and immunoglobulin secretion. Recombinant Human IL-1 beta is produced by E.coli expression system, and is produced with raw materials of pharmaceutical applicable level. The host protein residue, nucleic acid residue and common pathogens are strictly controlled, and the production and quality management procedures of the product comply with GMP regulations to ensure the traceability of the production process and all raw materials.

Interleukin-12 (IL-12) is a heterodimeric cytokine with a variety of immunomodulatory functions. It is mainly produced by dendritic cells, macrophages, B lymphocytes, and other antigen-presenting cells (APCs). IL-12 has only one high-affinity receptor, which is mainly distributed on the surface of the activated CD8+ or CD4+ T cells and CD56+ NK cells. IL-12 regulates the differentiation of Th0 cells to Th1 cells, promotes the proliferation of Th1 cells, and induces the production of IFN-gamma by NK cells and T cells. This can improve the killing activity of NK cells and LAK cells and promote the formation of specific CTL cells, thus displaying a good anti-tumor effect. Recombinant Human IL-12 is expressed by mammalian cells, and is produced with raw materials of pharmaceutical applicable level. The host protein residue, nucleic acid residue and common pathogens are strictly controlled, and the production and quality management procedures of the product comply with GMP regulations to ensure the traceability of the production process and all raw materials.

Il-15 (Interleukin-15), is a member of the Il-2 cytokines family. Il-15 performs biological functions by γ c receptor subunits. Several therapies targeting solid tumor and blood cell tumor have entered the clinic study. Although both IL-2 and IL-15 are involved in early T cell proliferation and activation. The antitumor activity of IL-15 also comes from direct activation of CD8+ effector T cells in a non-specific antigen immunogenicity way. It is reported that there has been clinic study of IL-15 targeting immune cell therapy entering phase I. This product is from a large scale GMP leveled Recombinant Human Il-15 production via E. coli expression. Applying pharmaceutical leveled adjuvants and materials for production, strictly controlling host protein residues, nucleic acid residues, pathogene contamination and other impurities, we guarantee an auditable manufacture and quality control practice complying to GMP regulation, as well as all the materials traceable.

Interleukin-18 (IL-18) is a member of the IL-1 family. Its ability to induce the production of IFN-gamma is even stronger than IL-12. IL-18 can stimulate the proliferation of CD3 monoclonal antibody-activated T cells. It also acts as an activator of NK cells to enhance the cytotoxic effect of NK cells. Also, IL-18 can act synergistically with IL-12 to induce the production of IFN-gamma, improving NK cell activity and promoting T cell proliferation. Recombinant Human IL-18 is expressed by mammalian cells, and is produced with raw materials of pharmaceutical applicable level. The host protein residue, nucleic acid residue and common pathogens are strictly controlled, and the production and quality management procedures of the product comply with GMP regulations to ensure the traceability of the production process and all raw materials.

IL-2, also known as T cell growth factor (TCGF), is the most important cytokine that causes T cell proliferation. IL-2 specifically binds to the IL-2 receptor (IL-2R) on the surface of T cells to activate T cells, for proliferation. Besides, IL-2 stimulates the growth of NK cells and enhances lethality of NK cells. IL-2, together with other T cell growth factors from the family activates and duplicates CD4+ and CD8+T cells by the common receptors. IL-2 activates T cells and NK cells by autocrine and paracrine modes. Unlike T cells, NK cells do not express alpha receptor subunit and therefore have a low affinity for IL-2. However, IL-2 can promote NK cell proliferation, enhance cell activity and generating other cytokines. B cells are also activated by IL-2, which leads to proliferation and cell differentiation. Recombinant Human IL-2 is expressed by mammalian cells, and is produced with raw materials of pharmaceutical applicable level. The host protein residue, nucleic acid residue and common pathogens are strictly controlled, and the production and quality management procedures of the product comply with GMP regulations to ensure the traceability of the production process and all raw materials.

IL-21, is a kind of Type I Cytokine, highly homogeneous with IL-2, IL-4, IL-15, etc, sharing γ c receptor subunit and cytokine specific receptor Alpha subunit with IL-7 and IL-9. In vivo IL-21 is produced by activated CD4+T cells and has various bioactivities, stimulating CD4+ and CD8+T cell proliferation and NK cell toxicity without triggering activation-induced apoptosis. Although the mechanism of IL-21 in Th1/Th2 differentiation is not clear yet, IL-21 plays an important role in humoral immunity and regulating natural/acquired immunity. Due to the important function of IL-21 in enhancing the proliferation and differentiation of antigen specific T cells in vitro, it has been more and more widely applied in immune cell therapy. Recombinant Human IL-21 is produced by E.coli expression system, and is produced with raw materials of pharmaceutical applicable level. The host protein residue, nucleic acid residue and common pathogens are strictly controlled, and the production and quality management procedures of the product comply with GMP regulations to ensure the traceability of the production process and all raw materials.

Interleukin-4 (IL-4) is a cytokine secreted by type II T helper cells (Th2 cells). It guides the monocytes to differentiate to DCs by inhibiting the growth of macrophages. Monocytes will differentiate to macrophages in a culture system without IL-4. IL-4 also reduces the expression of CD14 molecules on the cell surface, while the reduction in CD14 expression level is an important marker of the differentiation of monocytes into DCs. The biological effects of IL-4 include stimulating the proliferation of activated B cells and T cells, differentiation of CD4+ T cells into type II T helper cells, and stimulation of Th2 secretion of ,IL-4 IL-5, IL-6, IL-10, and IL-13. IL-4 also plays a critical role in regulating humoral immunity and adaptive immunity. It induces the switching of the B cell antibody class to IgE and upregulates MHC II production. Recombinant Human IL-4 is expressed by mammalian cells, and is produced with raw materials of pharmaceutical applicable level. The host protein residue, nucleic acid residue and common pathogens are strictly controlled, and the production and quality management procedures of the product comply with GMP regulations to ensure the traceability of the production process and all raw materials.

Interleukin-7 (IL-7), a member of the cytokine family related to IL-2, stimulates the survival, proliferation, and homeostasis of T cells via the gamma c (γc) subunit of the receptor. IL-7 can replace IL-2 for activating T cells and avoid the immune tolerance due to Treg activation by IL-2. Studies have shown that IL-7 can expand antigen-specific T cells in vaccine injection or cell therapy; in addition, IL-7 is able to promote T cell recovery after chemotherapy or hematopoietic stem cell transplant. Recombinant Human IL-7 is expressed by mammalian cells, and is produced with raw materials of pharmaceutical applicable level. The host protein residue, nucleic acid residue and common pathogens are strictly controlled, and the production and quality management procedures of the product comply with GMP regulations to ensure the traceability of the production process and all raw materials.

MHC class I peptide associated sequence A, also known as MICA, is a single channel type I membrane protein belonging to the MHC class I family of the MIC subfamily. MICA is a ligand for the NK cell activation receptor KLRK1/NKG2D, which can bind to the NKG2D receptor on the surface of NK cells, thereby activating the killing activity of NK cells.. Recombinant Human MICA is expressed by mammalian cells, and is produced with raw materials of pharmaceutical applicable level. The host protein residue, nucleic acid residue and common pathogens are strictly controlled, and the production and quality management procedures of the product comply with GMP regulations to ensure the traceability of the production process and all raw materials.

CD40L, also known as CD154, is a plasma membrane glycoprotein and differentiation antigen expressed on the surface of T cells. It stimulates the proliferation of B cells to secrete various immunoglobulins in the presence of cytokines. CD40L can induce the cytokines secretion of peripheral blood mononuclear cells, so produce anti-tumor activity. It also has a co-stimulatory effect on the proliferation of activated T cells, accompanied by the production of IFN-gamma, TNF-alpha, and IL-2. Recombinant Human sCD40L is expressed by mammalian cells, and is produced with raw materials of pharmaceutical applicable level. The host protein residue, nucleic acid residue and common pathogens are strictly controlled, and the production and quality management procedures of the product comply with GMP regulations to ensure the traceability of the production process and all raw materials.

TNF-alpha can downregulate the macropinocytosis and the expression of surface Fc receptors of immature DCs . It also upregulates the expression of MHC class I/II molecules and B7 family molecules (such as CD80 and CD86) on the cell surface, so that immature DCs differentiate to mature DCs. At this point, the antigen uptake and processing abilities of DCs decrease significantly while the antigen presentation ability of DCs increases significantly so that DCs can activate T cells in a very effective way. TNF stimulates IL-1 secretion of monocytes and macrophages, enhances the proliferation of IL-2-dependent thymic cells and T cells, promotes the production of lymphokines such as IL-2, CSF, and IFN-gamma, and enhances the proliferation and Ig secretion of B cells stimulated by mitogens or foreign antigens. TNF-alpha can kill certain tumor cells in vivo and in vitro, or inhibit proliferation. Treatment of tumor cells (such as mouse fibroblast line L929) with actinomycin D, mitomycin C, or cycloheximide can significantly increase the activity of TNF-alpha in killing tumor cells. This improves the phagocytic ability of neutrophils, increases the production of peroxide anions, enhances ADCC effect, and stimulates cell degranulation and secretion of myeloperoxidase. Recombinant Human TNF-alpha is expressed by E. coli, and is produced with raw materials of pharmaceutical applicable level. The host protein residue, nucleic acid residue and common pathogens are strictly controlled, and the production and quality management procedures of the product comply with GMP regulations to ensure the traceability of the production process and all raw materials.

Tscm Expander® is a mixing of cytokines (IL-7, IL-15, etc.) at a certain proportion. It specifically expands the T-memory stem cells and significantly extends the in vivo post-infusion survival time of T cells with specific killing ability, thus remarkably improving the efficacy of immune cell therapy against the tumor. In the traditional cell expansion procedures, after the monocytes activated by CD3/CD28 monoclonal antibodies are further expanded by IL-2, the majority of T cells highly differentiate to effector/memory T cells. These cells are weak in self-renewal ability with short post-infusion survival time in vivo, resulting in poor therapeutic effects. Tscm Expander® takes the place of IL-2 in the expansion of activated T cells so that 30% of the expanded T cells are transformed into T-memory stem cells. This greatly prolongs the post-transplant survival time of immune cells in vivo and improves the therapeutic effect. The T memory stem cell expanders of Tscm Expander® are produced with raw materials of pharmaceutical applicable level. The host protein residue, nucleic acid residue and common pathogens are strictly controlled, and the production and quality management procedures of the product comply with GMP regulations to ensure the traceability of the production process and all raw materials.