Tinostamustine and Anti-CD38 Antibody Combination for Multiple Myeloma
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Solution Overview
Problem
Current treatments for multiple myeloma using anti-CD38 antibodies face challenges due to off-target binding to normal cells, leading to adverse side effects and heterogeneous tumor expression, which results in relapse and refractory disease.
Innovation Solution
Combining tinostamustine with anti-CD38 antibodies to enhance CD38 expression on cancer cells, thereby improving the selectivity and efficacy of anti-CD38 therapies, including daratumumab, by increasing CD38 surface expression and activating innate immune responses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If anti-CD38 antibodies are administered at high doses intravenously to achieve therapeutic efficacy, then the therapeutic effect is improved, but adverse side effects increase due to off-target binding to normal cells
Solution Approach 1:
The patent applies preliminary action by administering tinostamustine before anti-CD38 antibodies to upregulate CD38 expression on cancer cells. This pre-treatment enhances the selectivity and efficacy of subsequent anti-CD38 antibody therapy, allowing for reduced dosing while maintaining therapeutic effect and minimizing off-target binding to normal cells.
2Productivity
If anti-CD38 antibodies are used to treat heterogeneous tumor expression, then initial treatment response is achieved, but relapse occurs due to CD38 heterogeneity in the tumor
Solution Approach 1:
The patent applies parameter changes by using tinostamustine to alter the expression level parameter of CD38 on cancer cells. This upregulation of CD38 expression makes heterogeneous tumor cells more uniformly susceptible to anti-CD38 antibody therapy, improving both initial response and preventing relapse by addressing the heterogeneity problem.
3Reliability
If high doses of anti-CD38 antibodies are administered to overcome low CD38 expression on cancer cells, then therapeutic efficacy is improved, but selectivity for cancer cells over healthy tissue decreases
Solution Approach 1:
The patent applies preliminary action by using tinostamustine to pre-upregulate CD38 expression on cancer cells before administering anti-CD38 antibodies. This sequence allows the antibodies to bind more effectively to cancer cells with enhanced CD38 expression, improving selectivity while maintaining therapeutic efficacy at lower doses.
Solution Approach 2:
The patent applies local quality by creating a difference in CD38 expression levels between cancer cells (upregulated by tinostamustine) and normal cells. This localized enhancement of CD38 expression on cancer cells improves the selectivity of anti-CD38 antibody binding, allowing the therapy to target cancer cells preferentially over healthy tissue.
Data Source
AI summary
The present invention relates to the use of tinostamustine or a pharmaceutically acceptable salt thereof in combination with one or more anti-CD38 antibodies in the treatment of cancer.