Focused Radiation for Immune Augmentation in Cancer Therapy

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Solution Overview

Problem

Current cancer therapies, including immunotherapy and radiation therapy, face limitations in effectively targeting tumor heterogeneity and immune evasion mechanisms employed by cancer cells, leading to marginal improvements in survival rates and associated toxicities.

Innovation Solution

A method involving the administration of a therapeutically effective dose of focused radiation to activate and maintain the immune system, combined with immunotherapeutic agents such as immune checkpoint inhibitors, to overcome tumor-mediated immune suppression and increase cancer antigen presence in the tumor microenvironment.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Volume of stationary object

If conventional radiation therapy is used to reduce tumor bulk, then tumor size is reduced, but radiation-associated toxicities increase and immune function is suppressed

Engineering Contradiction:

Improvetumor bulkVSAvoidradiation-associated toxicities

Core Design Contradiction:

Volume of stationary objectVSObject-affected harmful factors

Solution Approach 1:

The patent divides the radiation treatment into two distinct phases: (1) conventional radiation to reduce tumor bulk, and (2) focused radiation to eliminate residual cells while sparing normal tissue. This segmentation allows each radiation type to perform its optimal function without the downsides of using either approach alone.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent changes the radiation parameters by switching from conventional diffuse radiation to focused high-dose radiation. The focused radiation delivers a therapeutic dose concentrated on the tumor site while minimizing exposure to surrounding normal tissues, thereby reducing toxicities.

Inventive Principle:

Principle #35Parameter changes

2Volume of stationary object

If conventional radiation therapy is used to treat cancer, then tumor bulk is reduced, but immune suppression increases

Engineering Contradiction:

Improvetumor bulkVSAvoidimmune function

Core Design Contradiction:

Volume of stationary objectVSReliability

Solution Approach 1:

The treatment is segmented into phases where conventional radiation first reduces tumor bulk, followed by focused radiation that spares normal tissue and its immune cells. This segmentation prevents the cumulative immune suppression that would result from prolonged conventional radiation.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent converts the potential harm of radiation-induced immune suppression into a benefit by using focused radiation to create an immunogenic tumor environment. The high-dose focused radiation stimulates immune responses while the brief treatment duration prevents chronic immune suppression.

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

3Reliability

If immunotherapy is used to activate immune response, then anti-tumor immunity is enhanced, but tumor immune evasion mechanisms reduce effectiveness

Engineering Contradiction:

Improveimmune responseVSAvoidimmune suppression mechanisms

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent applies preliminary conventional radiation to reduce tumor bulk and alter the tumor microenvironment before administering immunotherapy. This preliminary action makes the tumor more susceptible to immune attack by reducing immunosuppressive factors and increasing antigen presentation.

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent changes the tumor microenvironment parameters through focused radiation, which induces immunogenic cell death and alters the expression of immune checkpoint molecules. This parameter change enhances the effectiveness of subsequent immunotherapy by creating a more favorable immune environment.

Inventive Principle:

Principle #35Parameter changes

4Object-affected harmful factors

If focused radiation is used to minimize toxicities, then normal tissue is spared, but treatment duration must be extended

Engineering Contradiction:

Improveradiation toxicitiesVSAvoidtreatment duration

Core Design Contradiction:

Object-affected harmful factorsVSLoss of time

Solution Approach 1:

The patent segments the treatment into a brief focused radiation phase following conventional radiation. The focused radiation is administered in a short course (e.g., single fraction or few fractions) to minimize the extended treatment duration while still achieving the goal of sparing normal tissue.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent applies a high dose of focused radiation in a partial treatment approach, concentrating the therapeutic effect on the residual tumor cells while accepting that a single high-dose treatment is sufficient to achieve the desired outcome without requiring prolonged therapy.

Inventive Principle:

Principle #16Partial or excessive action

Data Source

PatentUS9132281B2Focused radiation for augmenting immune-based therapies against neoplasms

Publication Date: 2015.09.15 JOHNS HOPKINS UNIVERSITY

AI summary

An approach combining immune-based therapies with focused radiation, including stereotactic radiation, to treat cancers is disclosed. The use of focused radiation primes the immune system in a similar manner to vaccines to augment immune-based therapies and can counteract the suppressive effects of a tumor. The combination of focused radiation and immune-based therapies, including administration of at least one immunotherapeutic agent, improves survival compared to each therapy alone and can, in some cases, lead to a durable cure. Accordingly, focused radiation can be an adjuvant for immune-based therapies for treating cancers.