Compositions and methods for enhancing immunotherapy and vaccine efficacy
A therapy and vaccine technology, applied in the direction of non-active ingredients of polymer compounds, drug combinations, medical raw materials derived from bacteria, etc.
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Embodiment I
[0163] This example demonstrates the improved efficacy of immune checkpoint blockers and prebiotics in a preventative setting.
[0164] From the FDA's list, five candidate materials were selected for initial screening. Melatonin, present in the pineal gland and gastrointestinal tract, regulates sleep cycles and circadian rhythms. Epigallocatechin gallate (EGCG) is a natural antioxidant found in plants. Fucoidan, oligofructose and inulin are plant polysaccharides widely used in food and dietary supplements. These candidate materials were first tested for their ability to improve the antitumor efficacy of alpha-PD-1 therapy in a preventive manner. WT Balb / c mice were treated with these materials via oral gavage one week before tumor inoculation ( figure 1 A). All these agents showed stronger antitumor efficacy in combination with α-PD-1 therapy than with α-PD-1 alone, and inulin showed the best efficacy ( figure 1 B and C). Combination of inulin with α-PD-1 prolonged anima...
Embodiment II
[0167] This example describes the improved efficacy of immune checkpoint blockers and prebiotics in a therapeutic setting.
[0168] Having identified inulin as a promising candidate, these agents were next tested in a therapeutic setting. After inoculation of Balb / c mice with CT-26 cells, tumor-bearing mice were treated by oral gavage from day 7 ( figure 2 A). Consistent with prophylactic treatment, inulin combined with α-PD-1IgG showed the strongest antitumor efficacy ( figure 2 B and C), and prolonged animal survival ( figure 2 D). Inulin also elicited significantly higher AH1-specific CD8 in PBMCs at days 18 and 24 + T cells ( figure 2 E-G).
Embodiment III
[0170] This example describes the dose effect of inulin and melatonin.
[0171] The dose effects of inulin and melatonin, which are the top 2 candidates identified above, were next examined. Halving the doses of inulin and melatonin (ie, inulin 60 mg and melatonin 50 mg / Kg) did not impair their efficacy against tumor growth in combination with α-PD-1 ( image 3 A, B), indicating a relatively wide therapeutic window for inulin and melatonin. Similar results were found in the frequency of AH1-specific CD8+ T cells in PBMCs ( image 3 C, D). Since tumor-infiltrating lymphocytes play a key role in the outcome of immunotherapy, T lymphocytes in the tumor microenvironment were examined. Inulin or melatonin treatment in combination with α-PD-1IgG significantly enhanced intratumoral infiltration of T cells compared with α-PD-1IgG alone ( image 3 E-H).
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