Search

JP-7856975-B2 - Antitumor immune response enhancer

JP7856975B2JP 7856975 B2JP7856975 B2JP 7856975B2JP-7856975-B2

Inventors

  • 蓮見 賢一郎
  • 梨井 康

Assignees

  • 蓮見 賢一郎
  • 国立研究開発法人国立成育医療研究センター

Dates

Publication Date
20260512
Application Date
20220912

Claims (8)

  1. An antitumor immune response enhancer containing phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine.
  2. An antitumor immune response enhancer according to claim 1, for use in suppressing tumor growth in a target area.
  3. An antitumor immune response enhancer according to claim 1, for use in converting immature dendritic cells into mature dendritic cells.
  4. An antitumor immune response enhancer according to claim 3, for use in converting immature dendritic cells into CD11b + CD11c + living cells.
  5. The antitumor immune response enhancer according to claim 4, characterized in that the immature dendritic cells are immature standard dendritic cells or tumor-associated dendritic cells.
  6. An antitumor immune response enhancer according to claim 1 or 2, characterized by containing 50-90% phosphatidylcholine, 5-25% phosphatidylethanolamine, and 5-25% phosphatidylserine.
  7. The antitumor immune response enhancer according to claim 1 or 2, further comprising one or more anticancer agents.
  8. A method for preparing mature dendritic cells by culturing immature dendritic cells in vitro in the presence of an antitumor immune response enhancer according to claim 1 or 2.

Description

This invention relates to an antitumor immune response enhancer, and more particularly to an antitumor immune response enhancer comprising phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine. Dendritic cells (DCs) are known to be the most potent antigen-presenting cells that can prime both naive T cells and memory T cells and induce antigen-specific antitumor immunity (see, for example, Non-Patent Document 1). However, DCs in the tumor microenvironment, i.e., tumor-associated dendritic cells (TADCs), are known to exhibit low expression of costimulatory molecules and immature phenotypes (see, for example, Non-Patent Document 2), or to exhibit suppressive and dysfunctional phenotypes, which can contribute to cancer cells escaping the host's immune surveillance network (see, for example, Non-Patent Document 3), thus potentially causing immunosuppression or immune tolerance. Furthermore, there are reports that TADCs secrete various types of cytokines that suppress the activation of antitumor-type T cells and promote tumor cell proliferation (see, for example, Non-Patent Document 4). Therefore, it is known that in the tumor microenvironment, DCs can be a double-edged sword, having both positive and negative effects on the antitumor response (see, for example, Non-Patent Document 5), and conventional cancer immunotherapy may result in reduced antitumor activity. On the other hand, a method for activating tumor-infiltrating lymphocytes (TILs) has been proposed (see, for example, Patent Document 1) that involves administering a fermentation composition produced through fermentation in a culture medium of symbiotic microorganisms to subjects requiring TIL activation. Furthermore, compositions for ex vivo dendritic cell activation containing one or more lipids having at least one cationic lipid and at least one antigen (see, for example, Patent Document 2), and the use of all-trans retinoic acid injections characterized by enabling the reduction of activity of abnormal myeloid-derived immunosuppressive cells, induction of differentiation of myeloid-derived immunosuppressive cells, and suppression of tumor growth and recurrence in tumor patients (see, for example, Patent Document 3), have also been proposed. Japanese Patent Publication No. 2021-517587Japanese Patent Publication No. 2022-36961Special table 2019-528315 publication Steinman RM, Banchereau J. Taking dendritic cells into medicine. Nature. 2007;449(7161):419-26Oncotarget. 2016;7(39):63204-14J Cancer. 2013;4(1):36-44J Leukoc Biol. 2017;102(2):317-324Frontiers in Oncology 2013 Volume 3 Article 90:1-12 (a) is a graph showing the changes in tumor volume up to 16 days post-transplantation in mice that received a subcutaneous injection of 4 mg/kg mouse body weight or 12 mg/kg mouse body weight of cPLs adjuvant in the flank after transplantation of MO4-Luc cells, and in control mice that did not receive cPLs adjuvant. The horizontal axis represents the number of days after transplantation, and the vertical axis represents the tumor volume in MO4-Luc cell transplanted mice. (b) is a histogram of tumor volume at 16 days post-transplantation in mice that received a subcutaneous injection of 4 mg/kg mouse body weight or 12 mg/kg mouse body weight of cPLs adjuvant, and in control mice that did not receive cPLs adjuvant. (c) is a graph showing the changes in tumor volume up to 16 days post-transplant in mice that received a subcutaneous injection of 12 mg/kg mouse body weight of cPLs adjuvant in the flank after C26 cell transplantation, and in control mice that did not receive cPLs adjuvant. (d) is a histogram of tumor volume at 16 days post-transplant in mice that received 12 mg/kg mouse body weight of cPLs adjuvant, and in control mice that did not receive cPLs adjuvant. (e) is a graph showing the changes in tumor volume up to 16 days post-transplant in MO4-Luc cell transplanted mice that were administered cPLs adjuvant, PC, PE, and PS, respectively.This shows flow cytometry analysis of standard mouse bone marrow dendritic cells cultured in the presence of cPLs adjuvant.This graph shows the expression of (a) IA/IE, (b) CD80, and (c) CD40 surface markers after culturing standard mouse bone marrow dendritic cells in the presence of cPLs adjuvants, expressed as the mean fluorescence intensity (MFI) delta (Δ) value.The graphs below show the expression of (a) IL-1β, (b) IL-12, and (c) IL-6 in imDCs cultured for 2 days in the presence of cPLs adjuvants, expressed as MFI delta values.Both (a) and (b) show flow cytometry analysis of TIL in the cPLs adjuvant-treated group.The graphs below show (a) the expression of CD86 and (b) the expression of IA/IE in the cPLs adjuvant-treated group, expressed as MFI delta values.This graph shows the expression of (a) IL-1β, (b) IL-12, and (c) IFN-γ in the cPLs adjuvant-treated group, expressed as the delta value of MFI.This graph shows the production of (a) IFN-γ, (c) TNF-α, and (e) IL-2 in CD4 + T cells, and the producti