CD38 Modulating Antibody for Solid Tumor Therapy
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Solution Overview
Problem
Current anti-CD38 antibodies are limited in their ability to target solid tumors due to lower or absent CD38 expression on tumor cells, and there is a need for antibodies that combine agonistic or modulating properties with targeted cell killing and pharmaceutical compatibility for effective cancer treatment.
Innovation Solution
Development of CD38 Modulating Antibody Agents that specifically bind to human CD38, modulating its activity and enhancing immune cell activation and proliferation, with specific binding affinities and epitope recognition, including antibodies like aCD38-a-323 and variants, which exhibit enhanced cytotoxic and activating properties.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional anti-CD38 antibodies are used to target tumors, then CD38-expressing cells can be killed, but the therapy is ineffective for solid tumors where CD38 expression is low or absent on tumor cells
Solution Approach 1:
The antibody is designed to perform multiple functions: it can bind to CD38 on immune cells to activate them (agonistic activity) while also enabling targeted killing of tumor cells through antibody-dependent cellular cytotoxicity (ADCC). This multi-functionality allows the same antibody to be effective across different tumor types regardless of CD38 expression levels on the tumor cells themselves.
Solution Approach 2:
The antibody uses immune cells as intermediaries to attack tumor cells. By activating immune cells through CD38 binding and recruiting them to the tumor site via ADCC, the antibody indirectly targets tumors that do not express CD38, using the immune system as a mediator to bridge the gap between the antibody and the tumor target.
2Ease of manufacture
If anti-CD38 antibodies are designed for direct tumor cell killing, then high CD38 expression on tumor cells is required, but this limits applicability to only certain cancer types
Solution Approach 1:
Instead of requiring the tumor cells to express the target antigen (CD38) for direct killing, the invention inverts the approach by targeting CD38 on immune cells and using the activated immune cells to kill the tumor cells. This reversal of the traditional target-killer relationship allows therapy to work on tumors regardless of their CD38 expression status.
3Device complexity
If CD38-targeting therapy relies on tumor cell CD38 expression, then mechanism is simple, but it fails when CD38 is absent or low on tumor cells
Solution Approach 1:
The invention merges two mechanisms into one therapeutic approach: CD38 agonism (activating immune cells through CD38 binding) and ADCC (recruiting immune cells to kill tumor cells). This combination ensures that even if one mechanism is less effective, the other can compensate, providing reliable therapeutic efficacy across different tumor types.
Data Source
AI summary
The present disclosure provides antibody sequences found in antibodies that bind to human CD38. In particular, the present disclosure provides sequences of anti-human CD38 antibodies. Antibodies and antigen-binding portions thereof including such sequences present features compatible with pharmaceutical manufacturing and development can be provided as fully human antibodies (e.g., fully human monoclonal antibodies or antigen-binding fragments) that can be useful for medical methods and compositions, in particular for treating cancer.