Chimeric VIP Antagonist Peptides for Immune Stimulation

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Solution Overview

Problem

Current cancer treatments, including surgery, chemotherapy, and radiation therapy, have limitations in effectively targeting and eliminating cancer cells, and there is a need for alternative therapies that enhance the immune system's ability to attack cancer cells.

Innovation Solution

The development of VIP antagonists, specifically chimeric peptides like VIPhyb and its variants, which are used to stimulate immune cells, such as T cells, to target and eliminate cancer cells by mixing these peptides with immune cells in vitro and administering them to patients.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If traditional cancer treatments (surgery, chemotherapy, radiation therapy) are used, then cancer cells can be treated, but the immune system's ability to attack cancer cells is not effectively enhanced

Engineering Contradiction:

Improvecancer cell elimination effectivenessVSAvoidimmune system activation capability

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent introduces VIP antagonists as intermediary substances that mediate between the immune system and cancer cells. These peptides block VIP receptors on cancer cells, preventing VIP from suppressing immune responses, thereby enabling the immune system to more effectively recognize and attack cancer cells without direct chemical cytotoxicity.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent replaces the mechanical/physical cancer treatment methods (surgery, radiation) with a biochemical mechanism involving VIP antagonist peptides. By using peptide-based molecular interference rather than physical removal or energy delivery, the treatment enhances the immune system's natural cancer-fighting capability.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

2Adaptability or versatility

If CAR T cell therapy is used to strengthen the immune system, then cancer cells can be targeted, but the complexity and difficulty of the treatment process increases

Engineering Contradiction:

Improveimmune system targeting capabilityVSAvoidtreatment process complexity

Core Design Contradiction:

Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent extracts and isolates the critical functional element needed for immune activation by removing VIP signaling inhibition. Instead of constructing complex engineered T cells, the treatment simply administers VIP antagonist peptides that naturally block VIP receptors, thereby simplifying the therapeutic approach while maintaining effective immune targeting.

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent employs simple, easily synthesized peptide molecules as the therapeutic agent rather than complex, expensive CAR T cell therapy. The VIP antagonist peptides are small, stable molecules that can be produced cost-effectively and administered repeatedly, reducing both the complexity and cost of treatment.

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

3Reliability

If VIPhyb peptide is used as a VIP antagonist, then T cell response can be enhanced, but the peptide stability and bioavailability may be limited

Engineering Contradiction:

ImproveT cell response enhancementVSAvoidpeptide stability in circulation

Core Design Contradiction:

ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent modifies the molecular parameters of the VIP antagonist by creating chimeric peptides that combine the N-terminal sequence of VIPhyb with the C-terminal sequence of native VIP. This parameter change in the peptide structure optimizes both the antagonistic activity at VIP receptors and the stability/bioavailability in the circulatory system.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent creates a composite peptide structure that combines functional elements from different parent peptides (VIPhyb and native VIP) into a chimeric molecule. This composite structure integrates the beneficial properties of both parent sequences, achieving both effective T cell stimulation and improved pharmacokinetic properties.

Inventive Principle:

Principle #40Composite materials

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 use of VIP antagonists, particularly ANT-8, has shown enhanced T-cell proliferation and anti-leukemia responses in murine models, indicating improved immune stimulation and potential therapeutic efficacy against cancer.

Implementation Method 1

VIP functions as a bronchodilator. VIP also has the ability to alter cellular proliferation and the production of inflammatory signals through the VIP receptors VPAC1 and VPAC2.

Methodology Applied

Scientific EffectReceptor binding:

Data Source

PatentUS20250122258A1Compositions and uses of vasoactive intestinal peptide (VIP) antagonists

Publication Date: 2025.04.17 EMORY UNIVERSITY

AI summary

This disclosure relates to VIP antagonist for uses in managing the treatment or prevention of cancer and viral infections. In certain embodiments, this disclosure relates to chimeric variants of VIP antagonists, as peptides disclosed herein, and pharmaceutical composition comprising the same. In certain embodiments, this disclosure contemplates methods of stimulating immune cells to target cancer by mixing immune cells in vitro with peptides disclosed herein and further administering an effective amount of stimulated immune cells to a subject in need of cancer treatment.