Recombinant EGFL7 Antibodies Targeting AML Blast Growth
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Solution Overview
Problem
Current treatments for acute myeloid leukemia (AML) lack effective prognostic markers and therapeutic options, particularly for cytogenetically normal AML, where increased microRNA-126-3p expression is associated with shorter survival, and the role of its host gene, EGFL7, in AML biology remains unexplored.
Innovation Solution
Development of recombinant EGFL7 and EGFL7 antibodies, such as parsatuzumab, which target the EGF/DSL domain, for treating AML by inhibiting EGFL7 activity, and using EGFL7 expression levels to predict responsiveness to therapeutic agents, as well as expanding hematopoietic stem and progenitor cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current treatments for AML are used, then treatment is provided, but effective prognostic markers and therapeutic options are lacking
Solution Approach 1:
The patent performs preliminary identification and characterization of EGFL7 as a prognostic marker in AML before clinical application. Through preclinical studies and mechanistic investigations, the patent establishes EGFL7's role in AML biology, leukemic stem cell maintenance, and treatment resistance, creating a foundation for future clinical prognostic and therapeutic applications
Solution Approach 2:
The patent introduces EGFL7 as an intermediary biomarker that connects AML disease characteristics with patient prognosis and treatment response. By targeting EGFL7 with antibodies like parsatuzumab, the patent creates a mediatorial therapeutic approach that addresses multiple aspects of AML pathogenesis including stem cell maintenance and treatment resistance
2Object-affected harmful factors
If EGFL7 antibodies are administered, then AML blast growth is inhibited and apoptosis is induced, but potential side effects on normal hematopoiesis may occur
Solution Approach 1:
The patent exploits the localized overexpression of EGFL7 in AML blasts and leukemic stem cells compared to normal hematopoietic cells. By targeting EGFL7 specifically, the antibody therapy achieves selective anti-leukemic effects while sparing normal hematopoiesis, as evidenced by the differential expression patterns observed in AML versus normal bone marrow
Solution Approach 2:
The patent utilizes the dynamic regulation of EGFL7 expression in AML, particularly its upregulation in response to treatment stress and its role in adaptive resistance. The antibody therapy dynamically targets this evolving target, adapting to the leukemia's changing expression patterns while maintaining therapeutic efficacy
3Stability of the object's composition
If miR-126 expression is increased, then leukemia stem cell homeostasis is maintained, but overall survival is shortened
Solution Approach 1:
The patent converts the harmful effect of miR-126/EGFL7-mediated leukemia stem cell maintenance into a therapeutic opportunity. By targeting EGFL7 with antibodies, the therapy exploits the very mechanism that maintains LSC homeostasis to eliminate these cells, transforming the leukemia's dependency on EGFL7 into its vulnerability
Solution Approach 2:
The patent changes the critical parameter of EGFL7 expression levels through antibody-mediated suppression. By reducing EGFL7 expression and activity, the therapy disrupts the miR-126/EGFL7 axis that maintains LSC homeostasis, leading to loss of LSC function and improved survival despite the initial protective role of this pathway
Data Source
AI summary
The present disclosure relates to recombinant EGFL7, EGFL7 antibodies, and uses thereof.