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

ABSTRACT: Hematological malignancies express high levels of CD47 as a mechanism of immune evasion. CD47-SIRP? triggers a cascade of events that inhibit phagocytosis. Preclinical research supports several models of antibody-mediated blockade of CD47-SIRP? 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? 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 (CD20-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? interaction in leukemia, lymphoma and multiple myeloma.

SUBMITTER: Russ A 

PROVIDER: S-EPMC6186508 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature