Abstract
Astragalus membranaceus polysaccharide (APS) components are main ingredients of TCM and have proven efficacy to activate T cells and B cells, enhancing immunity in humans. In this study, elevated cytokine and anti-PD-1 antibody titers were found in mice after immunization with APS. Therefore, phage-display technology was utilized to isolate specific anti-programmed death-1 (PD-1) antibodies from mice stimulated by APS and to confirm whether the isolated anti-PD-1 antibody could inhibit the interaction of PD-1 with the programmed death-ligand 1 (PD-L1), resulting in tumor growth inhibition. The isolated single-chain fragment variable (scFv) S12 exhibited the highest binding affinity of 20 nM to PD-1, completed the interaction between PD-1 and PD-L1, and blocked the effect of PD-L1-induced T cell exhaustion in peripheral blood mononuclear cells in vitro. In the animal model, the tumor growth inhibition effect after scFv S12 treatment was approximately 48%. However, meaningful synergistic effects were not observed when scFv S12 was used as a cotreatment with ixabepilone. Moreover, this treatment caused a reduction in the number of tumor-associated macrophages in the tumor tissue. These experimental results indirectly indicate the ability of APS to induce specific antibodies associated with the immune checkpoint system and the potential benefits for improving immunity in humans.
Highlights
Astragalus membranaceus, known as huang qi in Chinese, is a type of traditional Chinese medicine (TCM) commonly used as an immunomodulatory agent, and its extracts have been proven to effectively strengthen the immune system to treat pathological diseases and even cancer [1, 2]
Studies have demonstrated that in vaccine immunization, Astragalus membranaceus polysaccharide (APS) has great potential as a potent adjuvant, enhancing the effect of antigen presentation by improving the performance of class II major histocompatibility complex molecules, which facilitates lymphocyte proliferation, increases the number of antibodies in serum, and increases the secretion of cytokine [10, 11]. This echoes the immunomodulatory effects induced by APS to improve the state of humoral immunity by increasing the levels of immunoglobulin M (IgM) and immunoglobulin G (IgG) [12]
APS was extracted from A. membranaceus following a previously described method [19]
Summary
Astragalus membranaceus, known as huang qi in Chinese, is a type of traditional Chinese medicine (TCM) commonly used as an immunomodulatory agent, and its extracts have been proven to effectively strengthen the immune system to treat pathological diseases and even cancer [1, 2]. Studies have demonstrated that in vaccine immunization, APS has great potential as a potent adjuvant, enhancing the effect of antigen presentation by improving the performance of class II major histocompatibility complex molecules, which facilitates lymphocyte proliferation, increases the number of antibodies in serum, and increases the secretion of cytokine [10, 11]. This echoes the immunomodulatory effects induced by APS to improve the state of humoral immunity by increasing the levels of immunoglobulin M (IgM) and immunoglobulin G (IgG) [12]
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