イプへの誘導は、ADCP によって抗体医薬品の効果を増強させるこLife scienceる。

本研究では、まず M2 と M1 のマクロファージの ADCP 活性を比較

Healthcare, Drug development

ロファージが顕著に高い ADCP 活性を示すことを明らかにした。次て M2 タイプから M1 タイプへマクロファージの表現系を変換してEnhancing antibody-dependent cellular phagocytosis
by Re-educationof tumor-associated単独と同様にした。さらに
R848 を内封したリポソームでも、R848
育及び ADCP 活性の増強が確認できた。 R 848 リポソームを腫瘍移macrophages with resiquimod-encapsulated liposomes
黒田俊一

曽宮正晴

すると、腫瘍組織に蓄積することがわかり、さらに腫瘍組織内のマクDepartment of Biomolecular Science and Reaction, The Institute of Scientific and Industrial Research (SANKEN)込まれていることを確認した。R848 内封リポソームおよび抗 EGFR
Assistant Professor Masaharu Somiya

Researchmap https://researchmap.jp/masaharusomiya

Professor Shun’ichi Kuroda

Researchmap https://researchmap.jp/read0186039

植マウスでは、対照群のマウスと比較して顕著に腫瘍の増殖が抑制さは、腫瘍組織中のマクロファージが M2 から M1 に再教育されていであることが示唆された。

黒田俊一

Life science

Abstract
We developed the tumor-associated macrophage (TAM)-targeting liposomes encapsulating the TLR7/8 agonist resiquimod (R848).
The R848-liposomes can convert the phenotype of macrophages
from tumor-supportive M2 type to tumor-suppressive M1 type andthe resulting macrophages can efficiently engulf the targeting tumor cells in an antibody-dependent manner (antibody-dependent
cellular phagocytosis, ADCP). In vivo, R848-liposomes were accumulated into the tumor tissue of xenograft mice, and the combination with therapeutic antibody resulted in the shrink of the tumor.
We confirmed the reduction of tumor burden was associated withthe phenotypic change of TAMs in the tumor tissue.

▍ Background & Results
Macrophages are important therapeutic targets in cancer because the tumor-associated macrophages (TAMs) assist the tumor
英語版の記載（全文で430 単語前
cells for their growth, evasion
from immunity, and metastasis.
Thephenotype of TAMs is classified into two types: tumor-suppressive後）
M1 type and tumor-supportive M2 type. In many cancers, M2TAMs are the major fraction 「of ATAMs
these TAMs may support
bstrandact」
the progression of the tumor. Therefore, the conversion of M2TAMs into M1 type would build
the anti-tumor microenvironment
記載ここから→We
developed theand improve the anti-cancer therapeutics, especially the antibody
tumor-associatedmacrophagetherapeutics via the antibody-dependent
cellular phagocytosis(ADCP). Resiquimod (R848), an antagonist for TLR7/8, is known toliposomes
induce the M1 phenotype in(TAM)-targeting
macrophages. We tried to deliver
theR848 into TAMs in vivo and evaluated whether the treatment withencapsulating the TLR7/8 agonist
R848-encapsulating liposomes can improve the therapeutic effectof antibodies in the mice xenograftmodel. (R848).
We demonstratedthatresiquimodThe R848R848-liposomes can induce the M1 phenotype in the mouse-derived macrophages and enhance
the ADCPcan
againstconvert
multiple canliposomesthecer cell lines. After the intravenous injection, the R848-liposomes
phenotypeof inmacrophages
fromcould accumulate in the transplanted
tumorsthe mice. The combination of R848-liposomes and antibody therapeutics (anti-EGFR
tumor-supportivetype
to tumor-suppressive
M1 type and the resulting macrophages canantibody, clone 528) significantly
suppressed theM2
tumor
growthin
the tumor-bearing mice.

efficiently engulf the targeting tumor cells in an antibody-dependent manner (antibody-and Future
perspective
dependent
cellularphagocytosis, ADCP). In vivo, R848-liposomes were accumulated into the▍ Significance of the research
We demonstrated the TAM-targetingdeliveryof R848 using
tumor tissueof xenograft
mice,li-and the combination with therapeutic antibody resulted in theposomes could convert the TAMs from M2 to M1 phenotype andshrinkof the tumor.
We confirmed
the reduction of tumor burden was associated with theimprove the therapeutic effectof antibody
therapeutics
via theADCP.

phenotypic change of TAMs in the tumor tissue.
「Background & Results」

記載ここから→ Macrophages are important therapeutic targets in cancer because the tumorassociated macrophages (TAMs) assist the tumor cells for their growth, evasion from
P a t e n t
Tr e a t i s eimmunity, and metastasis. The phenotype of TAMs is classified into two types: tumorsuppressive
type and tumor-supportive
M2 type. ofInmany cancers,
M2-TAMs
are theLi, H; Somiya, M; Kuroda,
S. EnhancingM1
Antibody-dependent
Cellular Phagocytosis by Re-education
Tumor-associatedMacrophages
with Resiquimodencapsulated Liposomes. Biomaterials. 2021 Jan; 268:120601. doi: 10.1016/j.biomaterials.2020.120601.

major fraction of TAMs and these TAMs may support the progression of the tumor. Therefore,URLK e y w o r d liposome, DDS, macrophage, TLR antagonist, antibody therapeutics
the conversion of M2-TAMs into M1 type would build the anti-tumor microenvironment andimprove the anti-cancer therapeutics, especially the antibody therapeutics via the antibodydependent cellular phagocytosis (ADCP). Resiquimod (R848), an antagonist for TLR7/8, is