SIRPα-antibody fusion proteins stimulate phagocytosis and promote elimination of acute myeloid leukemia cells

Ponce, Laia Pascual; Fenn, Nadja C.; Moritz, Nadine; Krupka, Christina; Kozik, Jan-Hendrik; Lauber, Kirsten; Subklewe, Marion; Hopfner, Karl‐Peter

doi:10.18632/oncotarget.14500

Cited by 18 publications

(22 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…NI-1701, a BsAb that targets CD47 and CD19 was designed for B-cell lymphoma and refractory leukemia [61]. Other bispecific agents (LicMABs) have been produced by the binding domain of SIRPα to a tumor-targeting antibody such as anti-CD33 promoted elimination of AML tumor cells [67].…”

Section: Specificity Of Anti-cd47 Targeting Agentsmentioning

confidence: 99%

Role of CD47 in Hematological Malignancies

et al. 2020

View full text Add to dashboard Cite

CD47, or integrin-associated protein, is a cell surface ligand expressed in low levels by nearly all cells of the body. It plays an integral role in various immune responses as well as autoimmunity, by sending a potent "don't eat me" signal to prevent phagocytosis. A growing body of evidence demonstrates that CD47 is overexpressed in various hematological malignancies and its interaction with SIRPα on the phagocytic cells prevents phagocytosis of cancer cells. Additionally, it is expressed by different cell types in the tumor microenvironment and is required for establishing tumor metastasis. Overexpression of CD47 is thus often associated with poor clinical outcomes. CD47 has emerged as a potential therapeutic target and is being investigated in various preclinical studies as well as clinical trials to prove its safety and efficacy in treating hematological neoplasms. This review focuses on different therapeutic mechanisms to target CD47, either alone or in combination with other cell surface markers, and its pivotal role in impairing tumor growth and metastatic spread of various types of hematological malignancies.

show abstract

Section: Specificity Of Anti-cd47 Targeting Agentsmentioning

confidence: 99%

Role of CD47 in Hematological Malignancies

et al. 2020

View full text Add to dashboard Cite

show abstract

“…While T-cells are essential in the anti-leukemia immune response, the innate immune system and especially macrophages are playing a role in immune evasion as well. CD47 is expressed by normal cells to inhibit phagocytosis by binding to SIRPα on macrophages and has been shown to be overexpressed on various tumor cells including AML 103,104 . An increased rate of CD47 expression has also been linked to a higher rate of transformation to AML in MDS patients 105 .…”

Section: 3) Anti-cd47mentioning

confidence: 99%

Immune checkpoint-based therapy in myeloid malignancies: a promise yet to be fulfilled

Bewersdorf

Stahl

Zeidan

2019

Expert Review of Anticancer Therapy

View full text Add to dashboard Cite

Introduction: Immune system evasion is essential for tumor cell survival and is mediated by the immunosuppressive tumor microenvironment and the activation of inhibitory immune checkpoints. While immune checkpoint-based therapy yielded impressive results in several advanced solid malignancies such as melanoma and non-small cell lung cancer, its role in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) is still evolving. Areas covered: Here we review the immunology in the tumor microenvironment in the bone marrow and discuss the current preclinical and clinical data for immune checkpoint-based therapy in myeloid neoplasms. Expert opinion: Clinical trials of immune checkpoint inhibitors (ICI) in AML and MDS are still in early stages and reported results so far have been modest especially for monotherapy use in the refractory settings. However, there are preliminary data for synergistic effects for combination of multiple ICI with hypomethylating agents and conventional chemotherapy. ICI might also be effective in eradicating minimal residual disease and to prevent relapse following induction chemotherapy or hematopoietic stem cell transplant. Additional trials to provide insight into the efficacy and safety profile of immune checkpoint-based therapy, its optimal timing and potential combination with other types of therapy as well as identification of predictive biomarkers are needed.

show abstract

“…This antibody has now entered clinical trials in patients with AML and solid tumors. The significance of CD47 as a target in AML therapy was validated in further reports [ 123 , 124 ]. Recent clinical data from another phase 1B study indicates that a combination of vincristine and magrolimab, a first-in-class antibody targeting CD47, may be effective in the treatment of AML and MDS [ 125 ].…”

Section: Therapeutic Targeting Of Lscmentioning

confidence: 83%

Acute Myeloid Leukemia Stem Cells: The Challenges of Phenotypic Heterogeneity

Arnone

Konantz

Hanns

et al. 2020

Cancers

View full text Add to dashboard Cite

Patients suffering from acute myeloid leukemia (AML) show highly heterogeneous clinical outcomes. Next to variabilities in patient-specific parameters influencing treatment decisions and outcome, this is due to differences in AML biology. In fact, different genetic drivers may transform variable cells of origin and co-exist with additional genetic lesions (e.g., as observed in clonal hematopoiesis) in a variety of leukemic (sub)clones. Moreover, AML cells are hierarchically organized and contain subpopulations of more immature cells called leukemic stem cells (LSC), which on the cellular level constitute the driver of the disease and may evolve during therapy. This genetic and hierarchical complexity results in a pronounced phenotypic variability, which is observed among AML cells of different patients as well as among the leukemic blasts of individual patients, at diagnosis and during the course of the disease. Here, we review the current knowledge on the heterogeneous landscape of AML surface markers with particular focus on those identifying LSC, and discuss why identification and targeting of this important cellular subpopulation in AML remains challenging.

show abstract

SIRPα-antibody fusion proteins stimulate phagocytosis and promote elimination of acute myeloid leukemia cells

Cited by 18 publications

References 53 publications

Role of CD47 in Hematological Malignancies

Role of CD47 in Hematological Malignancies

Immune checkpoint-based therapy in myeloid malignancies: a promise yet to be fulfilled

Acute Myeloid Leukemia Stem Cells: The Challenges of Phenotypic Heterogeneity

Contact Info

Product

Resources

About