BCMA-PD-1 Antibody Combination for Tumor Immunity
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Solution Overview
Problem
Current cancer treatments, particularly immunotherapies, face challenges in breaking tolerance to self-antigens and inducing a robust anti-tumor response, with a need for more effective therapies that enhance anti-tumor immunity.
Innovation Solution
A combination of a therapeutically effective amount of an antibody that binds BCMA, conjugated to a cytotoxic agent as an immunoconjugate, and a therapeutically effective amount of an antibody that binds PD-1, either as an antagonist or conjugated to a cytotoxic agent, to enhance anti-tumor immunity by inducing immunogenic cell death and modulating the immune response.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional cancer treatments are used, then tumor growth may be controlled to some extent, but they fail to break tolerance to self-antigens and induce robust anti-tumor immune responses
Solution Approach 1:
The patent combines two distinct immunotherapeutic mechanisms: BCMA-targeted antibody-drug conjugates (ADCs) that induce immunogenic cell death, and PD-1 pathway blockade that removes T-cell inhibition. This merging of approaches creates a synergistic effect where the ADC kills tumor cells and releases antigens while the PD-1 antibody simultaneously enhances T-cell activation and proliferation, together breaking immune tolerance and inducing robust anti-tumor responses that neither agent achieves alone
Solution Approach 2:
The invention employs composite therapeutic agents: an antibody-drug conjugate comprising a BCMA-specific antibody linked to a cytotoxic payload, combined with a PD-1-specific antibody. This composite approach integrates multiple functions (targeted cell killing, antigen release, immune checkpoint blockade) into a unified treatment regimen that addresses both tumor elimination and immune system activation
2Duration of action of stationary object
If immunotherapies target immune system cells to generate memory effector cells, then more durable effects are achieved, but the ability to break tolerance to self-antigens remains a major hurdle
Solution Approach 1:
The BCMA-targeted ADC performs preliminary action by killing tumor cells and releasing tumor antigens before the PD-1 antibody can fully activate T-cells. This antigen release creates the necessary conditions for subsequent T-cell recognition and activation, effectively preparing the immune system to respond to tumor antigens that would otherwise remain sequestered within viable tumor cells
Solution Approach 2:
The invention converts the harmful suppression of T-cells by PD-1 ligands into a beneficial effect. By blocking the PD-1 pathway, the treatment transforms the normally inhibitory interaction into an activating one, allowing T-cells to recognize and attack tumor cells with enhanced efficacy while generating durable memory responses
Data Source
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AI summary
Disclosed herein are combinations of an antigen binding protein that binds BCMA with a antigen binding protein that bind to an immunomodulatory agents, such as PD-1 or OX40, pharmaceutical compositions thereof, uses thereof, and methods of treatment comprising administering said combinations, including uses in cancer.