Nanosecond Pulsed Electric Fields for Tumor Immune Response
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Solution Overview
Problem
Current surgical methods for treating melanoma and other cancers are invasive, time-consuming, and often result in scarring, with internal tumors being particularly difficult to detect and treat, and there is a need for a safe and effective treatment that can address multiple tumors without individual excision.
Innovation Solution
The use of nanosecond pulsed electric fields (nsPEF) to stimulate an immune response by causing calreticulin expression on tumor cells, allowing the immune system to target and treat cancer cells, including metastasized tumors, through the application of sub-microsecond pulsed electric fields and the use of CD47-blocking antibodies.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If surgical excision is used to treat tumors, then tumors can be removed, but it results in infection risk, scarring, and is time-consuming for multiple tumors
Solution Approach 1:
The treatment process is segmented into two distinct phases: (1) nsPEF treatment phase that induces immunogenic apoptosis and triggers immune response in treated and untreated tumors, and (2) immune response phase where the patient's immune system naturally eliminates remaining tumor cells. This segmentation allows non-invasive treatment of multiple tumors simultaneously without sequential surgical procedures.
Solution Approach 2:
The patient's own immune system is harnessed to perform the tumor elimination function. By inducing immunogenic apoptosis through nsPEF treatment, the body's immune cells (particularly dendritic cells and T cells) are activated to recognize and destroy tumor cells autonomously, eliminating the need for external surgical intervention for each tumor.
2Reliability
If surgical excision is used to treat tumors, then tumors can be removed, but it causes infection and scarring
Solution Approach 1:
The mechanical surgical excision system is replaced with an electromagnetic field-based nsPEF treatment system. Instead of physically cutting and removing tumors with scalpels, the invention uses nanosecond pulsed electric fields to induce immunogenic apoptosis, thereby eliminating the mechanical trauma, bleeding, infection risk, and scarring associated with surgical procedures.
Solution Approach 2:
The body's immune system performs the tumor elimination function that would otherwise require surgical intervention. By triggering immunogenic apoptosis, the treatment leverages the patient's own immune cells to destroy tumor cells, eliminating the need for external surgical tools and procedures that cause physical damage and scarring.
3Reliability
If internal tumors are treated individually by surgery, then each tumor can be removed, but it is difficult to detect and treat all tumors
Solution Approach 1:
The nsPEF treatment system is designed to treat multiple tumors of varying sizes and locations simultaneously through a single application. The electric field can penetrate tissue and affect all tumor cells within the treatment zone, regardless of their depth or precise location, making the treatment universal and applicable to internal tumors that would be difficult to access surgically.
Solution Approach 2:
The immune system serves as a universal detection and elimination mechanism for all tumor cells in the body. Once triggered by nsPEF treatment of visible tumors, the immune response systematically searches for and eliminates other tumor cells throughout the body, including internal tumors that may not be detectable by imaging, thereby providing complete treatment without needing to individually locate and treat each tumor.
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
This method effectively triggers immunogenic apoptosis in tumor cells, stimulating an immune response that can target not only the treated tumor but also metastasized tumors, reducing the need for individual treatment of each tumor and potentially preventing chemotherapy, while monitoring immune response biomarkers to adjust treatment.
Implementation Method 1
treating a tumor with nanosecond pulsed electric fields (nsPEF) sufficient to cause the tumor to express calreticulin on surface membranes of its tumor cells
Implementation Method 2
applying, using the electrodes, sub-microsecond pulsed electric fields to the tumor sufficient to trigger immunogenic apoptosis in the tumor
Data Source
AI summary
Nanosecond pulsed electric field (nsPEF) treatments of a tumor are adjusted based on a size and type of the tumor to stimulate an immune response against the tumor and other tumors in the subject. Calreticulin expression on tumor cells can be detected to confirm treatment. An immune response biomarker can be measured, and further nsPEF treatments can be performed if needed to stimulate or further stimulate the immune response. Cancers that have metastasized may be treated by directly treating a tumor that is most accessible. The treatment can be combined with CD47-blocking antibodies, doxorubicin, CTLA-4-blocking antibodies, and/or PD-1-blocking antibodies. Electrical characteristics of nsPEF treatments can be based on the size, type, and/or strength of tumors and/or a quantity of tumors in the subject.