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Therapeutic antibody targeting of CD47 eliminates human acute lymphoblastic leukemia
Mark P Chao1, Ash A Alizadeh, Chad Tang
1Institute for Stem Cell Biology and Regenerative Medicine, Stanford Cancer Center, and Ludwig Center at Stanford, Palo Alto, California, USA. mpchao@stanford.edu
Insights
Researchers identified CD47 as a promising antibody target for acute lymphoblastic leukemia (ALL). Targeting CD47 enhanced the immune system
Area of Science:
- Oncology
- Immunology
- Hematology
Background:
- Acute lymphoblastic leukemia (ALL) is a common cancer in children and adults.
- Current treatments like chemotherapy have limitations and side effects.
- Targeted therapies, including monoclonal antibodies, are being explored for ALL.
Purpose of the Study:
- To identify novel antibody targets for acute lymphoblastic leukemia (ALL).
- To investigate the role of CD47 as a potential therapeutic target in ALL.
- To evaluate the efficacy of anti-CD47 antibodies in preclinical ALL models.
Main Methods:
- Analysis of CD47 expression in human ALL patient samples.
- In vitro studies assessing the effect of anti-CD47 antibodies on phagocytosis.
- In vivo studies evaluating anti-CD47 antibody efficacy in mouse models of ALL.
Main Results:
- CD47 is highly expressed on a subset of ALL cells and predicts poor outcomes.
- Anti-CD47 antibody treatment promoted phagocytosis of ALL cells by macrophages.
- Anti-CD47 therapy demonstrated significant efficacy in eliminating ALL in mice.
Conclusions:
- CD47 is a viable antibody target for treating acute lymphoblastic leukemia.
- Anti-CD47 antibody therapy shows potential for improving ALL treatment outcomes.
- These findings support further development of anti-CD47 therapies for human ALL.
Abstract:
Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy and constitutes 15% of adult leukemias. Although overall prognosis for pediatric ALL is favorable, high-risk pediatric patients and most adult patients have significantly worse outcomes. Multiagent chemotherapy is standard of care for both pediatric and adult ALL, but is associated with systemic toxicity and long-term side effects and is relatively ineffective against certain ALL subtypes. Recent efforts have focused on the development of targeted therapies for ALL including monoclonal antibodies. Here, we report the identification of CD47, a protein that inhibits phagocytosis, as an antibody target in standard and high-risk ALL. CD47 was found to be more highly expressed on a subset of human ALL patient samples compared with normal cell counterparts and to be an independent predictor of survival and disease refractoriness in several ALL patient cohorts. In addition, a blocking monoclonal antibody against CD47 enabled phagocytosis of ALL cells by macrophages in vitro and inhibited tumor engraftment in vivo. Significantly, anti-CD47 antibody eliminated ALL in the peripheral blood, bone marrow, spleen, and liver of mice engrafted with primary human ALL. These data provide preclinical support for the development of an anti-CD47 antibody therapy for treatment of human ALL.
