CD27-CD70 Interaction Detection in Renal Cell Carcinoma
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Solution Overview
Problem
Current treatments for renal cell carcinoma (RCC), particularly clear cell RCC, face challenges due to the aberrant expression of CD70, leading to immune evasion and metastasis, with limited understanding of the CD27-CD70 interaction's role in tumor microenvironment and its impact on immune response.
Innovation Solution
A method to determine the interaction between CD27 and CD70 by measuring soluble CD27 levels in biological samples, comparing them to predetermined reference values, to predict immune dysfunction and potential therapeutic targets in RCC.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If anti-angiogenic therapies targeting VEGF signaling axis are used to treat metastatic RCC, then tumor vascularization is inhibited, but immune evasion mechanisms remain unaddressed
Solution Approach 1:
The patent combines anti-angiogenic therapy (bevacizumab) with immunomodulatory therapy targeting the CD27-CD70 axis. This merging of two different therapeutic mechanisms addresses both tumor vascularization and immune evasion simultaneously, thereby improving overall treatment efficacy and versatility against metastatic RCC.
Solution Approach 2:
The therapeutic composition is designed to perform multiple functions: inhibiting VEGF signaling to prevent angiogenesis, blocking CD70 to prevent immune evasion, and activating CD27 to enhance immune response. This multi-functional approach allows a single treatment regimen to address multiple pathological mechanisms of RCC.
2Reliability
If CD70 expression is present on tumor cells, then T cell activation and proliferation are enhanced, but immune escape mechanisms are triggered
Solution Approach 1:
The patent exploits the dual nature of CD70 expression by using a blocking antibody to prevent the harmful immune escape mechanism while preserving or enhancing the beneficial T cell activation function. The blocking antibody converts the potentially harmful CD70-mediated immune escape into a beneficial state where T cell activation is maintained without the counterproductive immune suppression.
Solution Approach 2:
The blocking antibody acts as an intermediary that modulates the CD27-CD70 interaction. By binding to CD70, the antibody mediates a change in the interaction dynamics, preventing the harmful immune escape signal while allowing controlled T cell activation through alternative pathways or regulated CD27 engagement.
3Measurement precision
If soluble CD27 levels are measured to determine CD27-CD70 interaction, then immune dysfunction can be predicted, but the mechanism of interaction remains unclear
Solution Approach 1:
The patent uses soluble CD27 levels as a feedback marker to monitor the CD27-CD70 interaction status. By measuring sCD27 in biological samples and comparing to reference values, the system provides quantitative feedback about the extent of interaction, enabling prediction of immune dysfunction and treatment response while maintaining a clear mechanistic framework.
Data Source
AI summary
Inventors have shown that CD70 and CD27 are highly expressed in ccRCC and correlates with poor survival. Multiplex IF demonstrated that CD27+T cells interact with CD70+ tumor cells in tumor microenvironment (TME). CD27+T cells are more apoptotic than CD27−T cells in ccRCC. Elevated levels of plasma sCD27 is observed in ccRCC patients and correlates with CD27−CD70 interaction in situ. Their study demonstrates that CD27−CD70 interaction contributes to the release of sCD27 in peripheral blood in ccRCC, indicating that sCD27 is a potential biomarker. The apoptosis of CD27+T cells suggests the deleterious effect of CD27−CD70 interaction in T cell response. Therefore, CD27/CD70 is a promising therapeutic target in ccRCC. Accordingly, the invention relates to a method for determining the interaction between CD27 and CD70 by determining the level of soluble CD27 (sCD27) in a biological sample and to method of targeting CD27/CD70 interaction to treat a cancer or metastatic cancer.