Antibody-IR700 Conjugate NIR Photoimmunotherapy for Selective Cancer Cell Killing
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Solution Overview
Problem
Current cancer therapies often fail to selectively target and kill cancer cells while sparing non-cancerous cells, leading to side effects and autoimmune adverse events, and existing photodynamic therapies are limited by non-targeted photosensitizers causing harm to normal tissues.
Innovation Solution
The use of antibody-IR700 molecules conjugated with near-infrared (NIR) light to selectively kill cancer cells by binding to tumor-specific antigens and inducing necrotic cell death, combined with CTLA4 or PD-L1 antibody-IR700 molecules and reducing agents to minimize side effects and enhance immunotherapy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional cancer therapies (surgery, radiation, chemotherapy) are used to kill tumor cells, then cancer cells are effectively killed, but non-cancerous cells are also harmed causing side effects
Solution Approach 1:
The patent uses monoclonal antibodies as intermediaries that specifically bind to tumor-associated antigens on cancer cells. These antibody-photosensitizer conjugates deliver the photosensitizing agent selectively to cancer cells through the antibody's specific binding, acting as a mediator that targets the therapeutic effect to cancer cells while sparing normal cells. The antibody serves as the intermediary between the photosensitizer and the cancer cell surface antigen.
Solution Approach 2:
The patent applies local quality by concentrating the photosensitizing effect specifically at the location of cancer cells. The monoclonal antibody directs the photosensitizer to bind only to cancer cells expressing the target antigen, creating a localized high concentration of photosensitizer at the tumor site. When NIR light is applied, cell death occurs only in the localized region where the antibody-photosensitizer complex is bound, not in surrounding normal tissues.
2Productivity
If non-targeted photosensitizers are used in photodynamic therapy to kill cancer cells, then cancer cells are killed, but normal tissues are also harmed causing side effects
Solution Approach 1:
The monoclonal antibody acts as a targeting intermediary that guides the photosensitizer to cancer cells. Instead of using non-specific photosensitizers that distribute throughout the body, the antibody-photosensitizer conjugate uses the antibody's antigen-binding capability to deliver the photosensitizer selectively to cancer cells, eliminating the need for non-targeted photosensitizer distribution.
Solution Approach 2:
The patent changes the distribution parameter of the photosensitizer from non-specific systemic distribution to specific tumor-localized distribution. By conjugating the photosensitizer to a monoclonal antibody with high affinity for tumor antigens, the photosensitizer's biodistribution is fundamentally altered to concentrate at the tumor site while minimizing presence in normal tissues.
3Reliability
If high doses of monoclonal antibodies are used for targeted therapy to ensure sufficient binding to cancer cells, then cancer cell targeting is improved, but dose-limiting toxicity occurs due to biodistribution and catabolism
Solution Approach 1:
The patent merges the monoclonal antibody with a photosensitizer to create a dual-function conjugate. The antibody provides specific targeting to cancer cells, while the photosensitizer provides the therapeutic killing mechanism. This combination allows the use of lower antibody doses because the photosensitizer amplifies the killing effect locally at the binding site, reducing the need for high systemic antibody doses and their associated toxicities.
Solution Approach 2:
The patent utilizes the phase transition of the photosensitizer upon NIR light irradiation. The photosensitizer remains inert during circulation and binding, then undergoes a functional phase change when activated by NIR light, generating reactive oxygen species that kill the cancer cell. This allows the antibody-conjugate to circulate safely at low doses, then exert potent local cytotoxic effect only upon light activation at the tumor site.
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 approach effectively kills cancer cells with minimal harm to non-cancerous cells, reduces side effects like edema and autoimmune reactions, and promotes immunogenic cell death, achieving significant tumor reduction and improved survival rates.
Implementation Method 1
Following antibody localization of the APC to a tumor cell surface antigen
Implementation Method 2
NIR light is used to induce highly selective cytolysis. NIR-PIT induces rapid, necrotic cell death that yields innate immune ligands
Implementation Method 3
activation by NIR light causes physical changes in the shape of antibody-antigen complexes that induce physical stress within the cellular membrane
Data Source
AI summary
Provided herein are methods of treating a subject with cancer using a therapeutically effective amount of one or more one or more tumor-specific antibody-IR700 molecules. The methods can further include administering to the subject a therapeutically effective amount of (a) one or more CTLA4 antibody-IR700 molecules, one or more PD-L1 antibody-IR700 molecules, or combinations thereof, (b) one or more reducing agents, (c) one or more immunoactivators, or combinations of a, b, and c, for example, either simultaneously or substantially simultaneously with the tumor-specific antibody-IR700 molecules, or sequentially (for example, within about 0 to 24 hours). The method also includes irradiating the subject or cancer cells in the subject (for example, a tumor or cancer cells in the blood) at a wavelength of 660 to 740 nm at a dose of at least 1 J/cm2. The use of one or more reducing agents can reduce edema resulting from treatment.