NK Cell Activator-OK432

Note: NK cell activation reagent

Background

OK-432 is an immunomodulatory reagent prepared from the lyophilized, penicillin-inactivated Su strain of Group A Streptococcus pyogenes. In peripheral blood mononuclear cell (PBMC) cultures, OK-432 activates myeloid cells (monocytes/macrophages and dendritic cells), which subsequently release IL-12 and other cytokines that drive natural killer (NK) cell activation. Activated cells exhibit increased IFN-γ production, degranulation, and cytotoxic activity. OK-432 can also enhance neutrophil-mediated tumoricidal effects (e.g., via CD11b/CD18–ICAM-1 interactions) and induce LAK-like activity in lymphocytes. Owing to these immunostimulatory properties, OK-432 is widely used in vitro as a research-use-only NK-cell activator for NK/LAK activation workflows, ADCC assay development, dendritic-cell maturation, and tumor-immunology studies.

Specifications

Immunomodulatory Effects of OK432

• Neutrophil Activation: OK432-activated neutrophils can kill IFN-γ or TNF-α-treated cancer cells. It induces neutrophil-mediated cytotoxicity against autologous tumor cells through CD11b/CD18 and ICAM-1 binding.
• Monocyte-Mediated Tumor Killing: OK432-activated monocytes exhibit cytotoxic effects against autologous tumor cells, contributing to an anti-tumor immune response.
• NK Cell Activation: OK432 enhances NK cell activity by stimulating monocytes/macrophages to secrete IL-12, leading to NK cell-mediated tumor cytotoxicity.
• LAK (Lymphokine-Activated Killer) Cell Activity: After stimulation by OK432, lymphocytes exhibit potent LAK cell activity, even capable of targeting anti-NK tumor cells.
• Dendritic Cell Maturation: It upregulates the expression of co-stimulatory molecules (CD80/CD86), enhancing antigen presentation efficiency.
• Cytokine Release and Th1 Immune Response: OK432 significantly increases IFN-γ, TNF-α, and IL-6 secretion, driving Th1 polarization and strengthening anti-tumor immunity.
• Tumor Microenvironment Remodeling: OK432 suppresses regulatory T cell (Treg) activity and promotes tumor-associated macrophage (TAM) polarization to an anti-tumor M1 phenotype.

Direct Anti-Tumor Effects of OK432

• Tumor Cell Apoptosis Induction: OK432 activates the TLR4/MyD88 pathway, triggering caspase cascade-induced apoptosis in tumor cells.
• Anti-Angiogenesis: Suppresses VEGF expression, limiting tumor blood vessel formation and restricting tumor growth.
• Epigenetic Regulation: Downregulates DNA methyltransferase (DNMT) activity, reversing tumor suppressor gene silencing, such as p16.

With its multifaceted immunomodulatory and direct anti-tumor effects, OK432 is widely used in cancer immunotherapy, offering a promising approach to enhancing immune system responses against tumors.

References

1. Sakamoto N1,2, Ishikawa T3,4, Kokura S5,6, Okayama T7,8, Oka K9, Ideno M10, Sakai F11, Kato A12, Tanabe M13, Enoki T14, Mineno J15, Naito Y16, Itoh Y17, Yoshikawa T18.

2. Phase I clinical trial of autologous NK cell therapy using novel expansion method in patients with advanced digestive cancer. J Transl Med. 2015 Aug 25;13:277. doi: 10.1186/s12967-015-0632-8.

3. Pan K1, Lv L2, Zheng HX1, Zhao JJ1, Pan QZ1, Li JJ1, Weng DS1, Wang DD1, Jiang SS1, Chang AE3, Li Q3, Xia JC1. OK-432 synergizes with IFN-γ to confer dendritic cells with enhanced antitumor immunity. Immunol Cell Biol. 2014 Mar;92(3):263-74. doi: 10.1038/icb.2013.87. Epub 2013 Dec 3.

4. Sudo T1, Aruga A, Shimizu K, Matsushita N, Takasaki K. OK432-activated natural killer cells enhanced trastuzumab (Herceptin)-mediated antibody-dependent cellular cytotoxicity in patients with advanced cancer. Anticancer Res. 2006 Nov-Dec;26(6B):4327-33.

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OK432

OK432_SDS