Immunomodulatory composition and application thereof

Abstract

The invention discloses an immune regulation composition and application thereof. The composition comprises the following components (a), (b), (c), (d) and (e) or coding nucleic acids thereof: (a) IL-15, a mutant thereof or a functional fragment thereof; (b) IL-15 receptor alpha, a mutant thereof or a functional fragment thereof; (c) IL-12, a mutant thereof or a functional fragment thereof; (d) TGFBR2, a mutant thereof or a functional fragment thereof; and (e) PD1-CD80 fusion protein, a mutant thereof or a functional fragment thereof. The composition can synergistically improve the immune response of T lymphocytes.

Description

technical field [0001] The invention relates to the fields of immunology and medicine, in particular to an immunomodulatory composition and its application. Background technique [0002] Traditionally, tumor cell immunotherapy mainly stimulates the immune system through vaccination or adoptive cell immunotherapy, thereby triggering an immune response. This approach is based on the assumption that tumor-specific antigens are expressed by tumor cells and presented on the tumor cell surface by the major histocompatibility complex (MHC), while antitumor T cells are not sufficiently activated. Therefore, to address this issue, attempts have been made to either stimulate key positive co-immune and innate immune pathways such as CD28, CD40L (CD154) and various TLR receptors, or inhibit negative immunosuppressive pathways such as CTLA-4 The receptor, PD-1 receptor, increases the recognition of these antigens. [0003] Existing studies have shown that the expression of CD80 in canc...

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Problems solved by technology

[0007] However, after Sipuleucel-T went on the market, sales have been poor, and the original manufacturer, Dendreon Corporation, declared bankruptcy

Moreover, several other large-scale DC cell-based tumor vaccines have failed in phase III clinical trials

For example, Merck’s Stimuvax (targeting MUC1, renamed tecemotide in 2013) failed twice in phase III studies, and GlaxoSmithKline’s GSK1572932A (targeting MAGEA3) also stopped in clinical phase III. These data show that alone The use of DC vaccines usually does not lead to the expected improvement in the effect of immunotherapy, and satisfactory clinical results cannot be obtained

This may be due to the influence of various immunosuppressive factors, resulting in the failure of DC vaccine to induce enough anti-tumor T cells, which leads to clinical failure.

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