IndraLab

"Evasion of phagocytosis by myeloma cells can be achieved when PD-1 and SIRP-α anti-phagocytic receptors on the macrophage cell surface bind PD-L1 and CD47 ligands present on the MM cells, respectively xref , xref ( xref ))."

"In addition, SBsib-711 binds CD47 and PD-L1 on tumor cells, which is applicable in cancer immunotherapy as a checkpoint inhibitor."

"Regarding the expression of CD47 and PD-L1 in tumor cells, Casey et al. have demonstrated that MYC, which plays critical roles in stem cell maintenance and tumorigenesis, directly binds to the promote[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

"Several other IgG-based CD47-targeting bispecific antibodies have been developed, among others CD20-CD47 [ xref ] and CD70-KWAR23 [ xref ] CD47-CD19 [ xref , xref ], CD47-MSLN [ xref ], CD47-PDL1 [ xref , xref ], and PD-L1-SIRPα [ xref ]."

"These nanoparticles induced glioma-associated myeloid cell phagocytosis of tumor cells via CD47–PD-L1 ligation, and activation of T cell–supportive myeloid cell phenotypes due to STING agonist–mediated effects."

"The MYC transcription factor has been shown to upregulate CD47 and PD-L1 by binding to the promoters of CD47 and PD-L1 in mouse tumours thereby supressing the immune response and promoting tumour prog[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

"It has been revealed that c-MYC could promote CD47 and PD-L1 expression by binding to the promoters of CD47 and PD-L1 genes to suppress antitumor immune responses [ xref ]."

"Moreover, the synergistic binding of CD47 and PDL1 in anti–CD47-PDL1-ADN increases the chance of adhering it to the tumor tissue rather than interacting with normal cells."

"These include IMM2902 for CD47-Her2, IMM0306 for CD47-D20, and IBI322 for CD47-PD-L1."

"c-MYC promotes its expression by binding to the CD47–programmed cell death ligand 1 (PD-L1) promoter region in cells, regulating tumor immune microenvironment and anti-tumor response, which suggests t[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

"Binding activity of IMM2520 to PD-L1 and CD47."

"cMYC, a target of the canonical WNT pathway binds the promoters of the CD47 and PD-L1 genes."

"In HNSCC, PF-07257876 is a CD47-PD-L1 bispecific antibody, and a Phase I clinical trial is underway (NCT04881045)."

"Wang et al. designed a CD47-PD-L1 bi-specific antibody, named IB322 ( xref )."

"Taken together, these results suggest that melanoma-intrinsic SIRPA can effectively trigger T cell immunogenicity through CD47 interaction in PD-1/PD-L1 blockade immunotherapy."

"For example, MYC (MYC Proto-Oncogene, BHLH Transcription Factor) can involve in the recruitment of T cells and macrophages by directly binding to the promoter of CD47 (Cluster of Differentiation 47) and PDL1 (Programmed death-ligand 1), and then modify the microenvironment in tumor [ xref ]."

"MYC was found to bind directly to the promoters of the CD47 and PD-L1 genes."

"The anti-PD-L1-SIRPα fusion protein preferentially bound CD47 and PD-L1 on MC38 cells, with a major contribution from CD47 and a minor one from PD-L1 ( Figure 3 B)."

"We applied ChIP (Chromatin ImmunoPrecipitation)-Seq analysis to mouse MYC T-ALL cells ( xref ) and the human B cell line P493-6 ( xref , xref ) and found high levels of MYC bound to the promoter regions of the genes coding for CD47 and PD-L1 ( xref , xref )."

"Oncogenic levels of MYC bound the CD47 and PD-L1 gene promoters in human osteosarcoma U2OS cells, whereas low levels of MYC did not ( xref )."

"Don’t eat me signals include programmed death-ligand 1 (PD-L1), CD47, CD31, CD24, and major histocompatibility complex (MHC)-I, which bind to corresponding inhibitory receptors, including PD, signal regulatory protein (SIRP) α, CD31, Siglec10, and LILRB1 respectively [4]."

"The variable-domain from the PD-L1-blocking mAb #18 (CN Patent: 201810952740.3) was introduced in tandem onto h4C1 to generate a dual variable domain bsAb that binds bivalently to both CD47 and PD-L1 ( xref )."

"MYC upregulates expression of CD47 and PD-L1 on the tumor cell surface by directly binding to the promoters of 2 genes, CD47 and PD-L1 ( Casey, et al., 2016 )."

"The TIS granules can promote the association between the SET protein and membrane proteins to be translated, such as CD47 and PD-L1, through a mechanism that the 3′-UTRs of the mRNAs of the membrane proteins facilitate the interaction between SET and CD47 or PD-L1."

"Additionally, several well-designed BsAbs have been created, such as IMM2902 for CD47-Her2, IMM0306 for CD47-D20, and IBI322 for CD47-PD-L1, which effectively inhibit the CD47-SIRPα signal and enhance tumor cell phagocytosis without significant impact on RBCs [ xref , xref , xref , xref ] [ xref , xref , xref , xref ] [ xref , xref , xref , xref ]."

"A study demonstrated the use of bispecific antibodies constituted of CD47-PD-L1 called as IB322."

"The structural analysis of these complexes revealed the dominant contribution of the LCs to antigen binding, but also that the common HC provides some contacts in both CD47 and PD-L1 Fab complexes."

"The results of the experiment of the simultaneous interaction of antibodies with CD47 and PDL-1 are presented in xref ."

"Casey et al revealed that the MYC oncogene can regulate the antitumor immune response by directly binding to the promoters of the CD47 and programmed death ligand 1 (PD-L1) genes. xref Interleukin (IL)-6 has been demonstrated to upregulate CD47 expression on hepatoma cells by activating the signal transducer and activator of transcription 3 (STAT3) pathway. xref In addition, LMP1 upregulated c-myc via IL-6 induction followed by Jak3/STAT3 activation xref and it also upregulated PD-L1 via the STAT3, activator protein (AP)-1, and nuclear factor (NF)-kappa B pathways. xref Therefore, we infer that LMP1 may upregulate CD47 expression via the c-myc/IL-6/STAT3 pathway."

"According to previous literature summary, the CD47 and PD-L1 inhibitors, inhibitory CD47-PD-L1 fusion proteins, and reducing or knocking out CD47 and PD-L1 genes are the main methods to reduce protein[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

"In a recent study, IBI322 introduced as the other dual blocker of innate and adaptive immune checkpoints, collectively interacted with CD47 + PD-L1 + malignant cells but not with erythrocytes and show[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

"Mechanistically, MYC was shown to bind to the promoters of CD47 and PD-L1 as measured by chromatin immune-precipitation followed by sequencing (ChIP-Seq) [ xref ]."

"The CD47-SIRPα axis is an important innate immune checkpoint regulating the homeostatic clearance of aged or damaged cells by macrophages. xref , xref The interaction of CD47 with SIRPα promotes the localization of SIRPα to the phagocytic synapse, activating the src-homology-2 domain containing tyrosine phosphatases (SHP-1 and SHP-2), which ultimately inhibit myosin II accumulation at the phagocytic synapse, preventing engulfment. xref Interaction of CD47 on cell surfaces with SIRPα on phagocytes thus prevents the phagocytic elimination of healthy cells, serving as a “don’t eat me” signal. xref However, cancer cells have evolved to hijack the CD47-SIRPα axis by upregulating the expression of CD47 to evade macrophage-mediated immune surveillance. xref , xref Overexpression of CD47 was reported in both solid tumors and hematological malignancies. xref Accordingly, blockade of the CD47–SIRPa interaction is considered as a powerful means to activate the phagocytic clearance of tumor cells. xref , xref Therapeutic targeting of the SIRPα–CD47 pathway has been demonstrated to enhance the phagocytic uptake of tumor cells by macrophages in vitro and inhibit progression of malignancy in preclinical studies employing various types of tumors. xref , xref While many anti-CD47-SIRPα agents are being tested in clinical trials, xref the ubiquitous expression of CD47 limits the selective distribution of antibodies to tumors, leading to the risk of on-target toxicity resulting from phagocytosis of normal cells expressing CD47, including red blood cells (RBCs). xref Therefore, the development of a molecule that blocks tumor CD47 interaction with SIRPα on macrophages while minimizing its binding to CD47 on normal healthy cells is highly desirable. xref Recent reports describe next-generation CD47-blocking agents possessing such attributes. xref , xref In particular, bispecific antibodies (BsAb) targeting CD47 and tumor antigens, including NI-1701 for CD47-CD19, xref IMM0306 for CD47-CD20, xref and IBI332 for CD47-PD-L1, xref can selectively block CD47–SIRPα interaction and significantly enhance in vitro tumor cell phagocytosis, but with limited effect on RBCs."

"Binding of CD47 and PD-L1 to SIRPα on TAMs independently deliver antiphagocytic signals."

"Higher CD47 associated negatively with PDL1 and CTLA4 expression, as well as cytotoxic T-cells and dendritic cells but positively with TGF-beta, BRD4 and CXCR4/CXCL12 expression."