CD22-Δex5-6 Antibodies for Selective B-ALL Targeting
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Solution Overview
Problem
Current treatments for B-cell acute lymphoblastic leukemia (B-ALL) are inadequate, particularly for pediatric cases, due to the low mutational burden of pediatric B-ALL, limiting the development of effective immunotherapies, and there is a need for new therapeutic targets and methods to enhance treatment efficacy.
Innovation Solution
Development of antibodies and antibody derivatives that selectively bind to the CD22-Δex5-6 protein, a candidate cell surface immunotherapeutic target, which can be used alone or in conjunction with other anti-cancer agents such as chemotherapy, radiotherapy, or immunotherapy, and can include fusion proteins, chimeric antigen receptors, and monoclonal antibodies to induce cancer cell death and inhibit cancer cell growth.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional chemotherapy and immunotherapy are used for B-ALL treatment, then some cancer cells are killed, but treatment efficacy is limited due to low mutational burden and drug resistance develops
Solution Approach 1:
The patent extracts and targets a specific splice variant protein (CD22-Δex5-6) that is uniquely expressed in B-ALL cells but not in normal cells. This extraction of a specific therapeutic target allows for highly selective antibody therapy that bypasses the limitations of conventional chemotherapy and overcomes drug resistance by targeting a novel antigen rather than relying on mutational burden.
2Adaptability or versatility
If immunotherapy is developed for pediatric B-ALL, then treatment options are expanded, but the low mutational burden limits immunotherapy development
Solution Approach 1:
Instead of relying on the absence of mutations (low mutational burden) as a barrier to immunotherapy, the patent inverts the approach by targeting a specific splice variant protein that is abundantly expressed in B-ALL cells. This inversion transforms the therapeutic strategy from mutation-dependent immunotherapy to splice-variant-dependent antibody therapy, enabling effective immunotherapy despite low mutational burden in pediatric B-ALL.
3Object-affected harmful factors
If selective antibodies targeting CD22-Δex5-6 are developed, then cancer cell death is induced with high specificity, but development of new therapeutic targets is required
Solution Approach 1:
The patent applies parameter changes by targeting a specific post-translational modification state - the CD22-Δex5-6 splice variant protein - which differs from the full-length CD22 protein. This parameter change in protein expression (splice variant vs. full-length) provides a highly specific therapeutic target that can be selectively targeted by engineered antibodies, achieving high specificity for cancer cell death while using a target that is already part of the normal cell surface protein repertoire.
Data Source
AI summary
The present disclosure is directed to antibodies binding to CD22-Del.ex5-6 protein and methods of using such antibodies to treat cancers that express or overexpress CD22-Del.ex5-6 protein. Specifically, the disclosure provides a method of treating cancer comprising contacting a cancer cell in a subject with an antibody or antibody derivative that binds selectively to CD22-Del.ex5-6 protein, or to a peptide having the sequence of QLNVKHPPKKVTTVIQNP (SEQ ID NO: 1).