Blocking "don't eat me" signal of CD47-SIRPα in hematological malignancies, an in-depth review

被引：156

作者：

Russ, Atlantis ^{[1
]}

Hua, Anh B. ^{[2
]}

Montfort, William R. ^{[3
]}

Rahman, Bushra ^{[1
]}

Bin Riaz, Irbaz ^{[4
]}

Khalid, Muhammad Umar ^{[5
]}

Carew, Jennifer S. ^{[5
]}

Nawrocki, Steffan T. ^{[5
]}

Persky, Daniel ^{[5
]}

Anwer, Faiz ^{[5
]}

机构：

[1] Univ Arizona, Dept Med, Tucson, AZ USA

[2] Univ Arizona, Pharmacol & Toxicol, Tucson, AZ USA

[3] Univ Arizona, Chem & Biochem, Tucson, AZ USA

[4] Mayo Clin, Dept Med Hematol Oncol, Rochester, MN USA

[5] Univ Arizona, Arizona Canc Ctr, Dept Med, Div Hematol,Oncol, 1515 N Campbell Ave, Tucson, AZ 85724 USA

来源：

BLOOD REVIEWS | 2018年 / 32卷 / 06期

关键词：

CD47; Immunotherapy; Apoptosis; Phagocytosis; Leukemic stem cell; Monoclonal antibody; Hematologic malignancy; INTEGRIN-ASSOCIATED PROTEIN; ANTIBODY-MEDIATED PHAGOCYTOSIS; CD47 INDUCES APOPTOSIS; MONOCLONAL-ANTIBODY; STEM-CELLS; CALRETICULIN EXPOSURE; PROMOTE PHAGOCYTOSIS; REGULATORY PROTEIN; LEUKEMIA; MACROPHAGES;

D O I：

10.1016/j.blre.2018.04.005

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Hematological malignancies express high levels of CD47 as a mechanism of immune evasion. CD47-SIRP alpha triggers a cascade of events that inhibit phagocytosis. Preclinical research supports several models of antibody mediated blockade of CD47-SIRP alpha resulting in cell death signaling, phagocytosis of cells bearing stress signals, and priming of tumor-specific T cell responses. Four different antibody molecules designed to target the CD47-SIRP alpha interaction in malignancy are currently being studied in clinical trials: Hu5F9-G4, CC-90002, TTI-621, and ALX-148. Hu5F9-G4, a humanized anti-CD47 blocking antibody is currently being studied in four different Phase I trials. These studies may lay the groundwork for therapeutic bispecific antibodies. Bispecific antibody (CD2O-CD47SL) fusion of anti-CD20 (Rituximab) and anti-CD47 also demonstrated a synergistic effect against lymphoma in preclinical models. This review summarizes the large body of preclinical evidence and emerging clinical data supporting the use of antibodies designed to target the CD47-SIRP alpha interaction in leukemia, lymphoma and multiple myeloma.

引用

页码：480 / 489

页数：10

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