FAP-Targeted LIGHT Fusion Protein for Localized Tumor Immunotherapy
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Solution Overview
Problem
Existing cancer treatments targeting FAP-expressing cells suffer from systemic toxicity and limited efficacy, necessitating a more effective and less toxic approach.
Innovation Solution
A fusion protein comprising an antigen binding domain that specifically binds to FAP and a LIGHT protein or its fragment/variant, which promotes immune cell infiltration and tumor vessel normalization, enhancing anti-cancer effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If FAP-targeting immunotherapy is used, then anti-cancer efficacy is improved, but systemic toxicity increases
Solution Approach 1:
The fusion protein is designed to locally activate LIGHT protein signaling specifically at the tumor site through FAP binding, creating localized immune activation without systemic effects. The antigen binding domain ensures targeted delivery to FAP-expressing tumor cells, while the LIGHT protein fragment provides localized co-stimulation only where needed.
Solution Approach 2:
The invention extracts and utilizes only the essential functional domains of FAP-targeting antibodies and LIGHT protein, combining the antigen binding domain with a LIGHT protein fragment to create a minimal but effective fusion protein that achieves anti-cancer effects with reduced systemic toxicity.
2Reliability
If conventional cancer treatments are used, then tumor growth inhibition is achieved, but treatment efficacy is limited
Solution Approach 1:
The fusion protein merges the tumor-targeting capability of FAP antibodies with the immune-activating function of LIGHT protein, creating a dual-function therapeutic that simultaneously targets tumor cells and activates local immune responses, thereby enhancing overall treatment efficacy.
Solution Approach 2:
The fusion protein performs multiple functions: FAP binding for tumor targeting, LIGHT protein-mediated immune cell activation, and promotion of tertiary lymphoid structure formation. This multi-functionality addresses multiple aspects of cancer treatment simultaneously, improving overall efficacy.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The fusion protein efficiently targets cancer cells, promotes tertiary lymphoid structure formation, and normalizes blood vessels, providing effective cancer treatment with reduced systemic toxicity, especially when combined with an anti-PD-1 antibody.
Implementation Method 1
an antigen binding domain that specifically binds to FAP (fibroblast activation protein alpha)
Implementation Method 2
binds to and activates herpes virus entry mediator (HVEM/TNFRSF14) and lymphotoxin beta receptor (LTβR)
Implementation Method 3
enables effective treatment of cancer through efficient infiltration of immune cells into tumor tissue
Implementation Method 4
normalize blood vessels
Data Source
AI summary
A fusion protein comprising a LIGHT protein and an antigen-binding domain that specifically binds to FAP may exhibit anti-cancer effects. In particular, the fusion protein efficiently targets cancer cells which overexpress FAP, and LIGHT may bind to a lymphotoxin beta receptor and HVEM to promote the formation of tertiary lymphoid structures and normalize blood vessels. Accordingly, the fusion protein enables effective treatment of cancer through efficient infiltration of immune cells into tumor tissue. Furthermore, it was confirmed that the fusion protein of the present invention can treat cancer more effectively when administered in combination with an anti-PD-1 antibody compared to when administered individually.