System and Method for the Universal Destruction of Cancer Cells without Toxicity

Abstract

This invention provides tools and methods that prevent a cancer cell from growing and reproducing more cancer cells. The body's immune defenses are enabled to attack and destroy these cells if the cancer cell itself has not initiated its own natural apoptotic self-destruction processes. By addressing the increased rates of metabolism characteristic of all rapidly reproducing cancer cells using bio-nanotechnology to identify these hypermetabolizing cells, the cell's and the body's immune systems are empowered to eliminate the diseased cells. Preferably, the nano-sensor-particle not only binds external membrane receptors or lipid formations on the target cell, but also incorporates into the rapidly metabolizing cells acting to stop their growth and signal distress. The body's natural defenses are able to segregate and eliminate these cells.

Claims

1. A method of intercourse with a living cell in a human, said intercourse comprising at least one activity selected from the group consisting of: identifying said cell, targeting said cell, segregating said cell, isolating said cell and triggering a natural death in said cell, said method comprising: a) providing a component capable of carrying out chemical or physical monitoring of at least two parameters associated with a population comprising one or more living cells; b) activating a signal reporting at least one characteristic selected from the group consisting of: a physical property and a chemical property; and c) receiving said signal and correlating said signal with an indication of location of said cell.

2. The method of claim 1 wherein said at least two parameters comprise at least i) hydrogen ion concentration and ii) a temperature differential.

3. The method of claim 1 wherein said single component monitors at least one physical property and at least one chemical property.

4. The method of claim 3 wherein said at least one physical property comprises temperature.

5. The method of claim 3 wherein said at least one chemical property comprises a concentration of at least one ion.

6. The method of claim 5 wherein said at least one ion comprises a hydrogen ion.

7. The method of claim 1 wherein said monitoring is carried out by a plurality of substances.

8. The method of claim 7 wherein at least one of said plurality of substances is delivered by a nanosensor.

9. The method of claim 1 wherein said single component comprises a modified viral particle.

10. The method of claim 9 wherein said viral particle has been modified to increase cell interaction at increased hydrogen ion concentration.

11. The method of claim 9 wherein said viral particle has been modified to increase cell interaction at increased temperature.

12. The method of claim 9 wherein said viral particle comprises an engineered viral coat.

13. The method of claim 9 wherein said viral particle contributes to a cytokinetic release.

14. The method of claim 13 wherein cells responsive to said cytokinetic release contribute to destruction of cells in localities of elevated temperature and lower pH.

15. The method of claim 9 wherein said viral particle is selected from the group consisting of: vaccinia, lentiparticle, herpes, influenza, adenoparticle and reovirus.

16. The method of claim 9 wherein said viral particle is selected from the group consisting of DNA viruses.

17. The method of claim 9 wherein said viral particle is selected from the group consisting of RNA viruses.

18. The method of claim 15 wherein said RNA is single stranded RNA.

19. The method of claim 18 wherein said RNA is double stranded RNA.

20. The method of claim 19 wherein said viral particle is selected from the group consisting of: picornaviruses, togaviruses, orthomyxoviruses, rhabdoviruses and retroviruses.

21. The method of claim 19 wherein said viral particle is selected from the group consisting of: reoviruses and birnaviruses.

22. The method of claim 16 wherein said DNA is single stranded DNA.

23. The method of claim 16 wherein said DNA is double stranded DNA.

24. The method of claim 22 wherein said viral particle is selected from the group consisting of: parvoviruses, annelloviruses and circoviruses.

25. The method of claim 22 wherein said viral particle is selected from the group consisting of: adenoviruses, herpesviruses, poxviruses and papoviruses.

26. The method of claim 21 wherein said viral particle comprises an orthomyxovirus.

27. The method of claim 26 wherein said orthomyxovirus is selected from the group consisting of: genus A, genus B, and genus C.

28. The method of claim 27 wherein said viral particle comprises a type A orthomyxovirus.

29. The method of claim 15 wherein said viral particle comprises a herpes particle, said particle comprising a modified HSV-1.

Description

ILLUSTRATIVE EXAMPLES

[0221] As a general process a cell or zone of cells presenting abnormal metabolism is identified. Cells manifesting only initial tendency towards hyperproliferation and/or cancer may be treated and directed back to mainstream metabolism. However, in extreme metabolic digressions, one or more cells may be directed to follow a normal systemic process of cell death.

[0222] For example, aberrant metabolism may be detected by one or more physical and/or chemical metabolic indicators such as a local temperature increase from the cellular or mitochondrial chemical activity and/or excess hydrogen ion (H.sup.+) production (resulting in a lowered pH). For increased specificity in identifying the cells progressing along a hyperproliferative or other hypermetabolic path, using a plurality of is should reduce off-target effects.

[0223] In essence chemical and/or physical signals are detected and used to target and correct altered metabolisms. The probe(s) would test whether a cell or zone presented an increased temperature (one indicator of excess or elevated metabolic activity). This probe may be sensitive to another factor such as a chemical presence. E.g., the probe may only bind a certain ligand at elevated temperature, may be activated by increased ion concentration—such as H.sup.+, and/or may be CO.sub.2 or O.sub.2 dependent.

[0224] So a probe or set of probes will test for factor A, temperature in this example, and then factor b, here pH. When both conditions exist, the probe(s) may become activated to steer corrective metabolic events or to eliminate cells that have progressed beyond corrective capabilities. The dual sensor probe may operate as a beacon merely signaling cells requiring return towards normal metabolism. This probe may then serve as a ligand or activator of another compound, a collector of energy, such as electromagnetic radiation and/or as a blocker preventing another molecule from supplying or further activating metabolism at the target cell.

[0225] As an example, one probe, e.g., a nanosensor probe, may be both pH and temperature sensitive, concentrating in or on a cell manifesting an above threshold temperature or a temperature exceeding those of near tissues. The temperature sensation and effect may be pH sensitive where, e.g., a lower temperature difference is flagged as pH decreases, may be activated to bind and/or to become active only below a pH threshold. The probe may distribute across a pH gradient favoring distribution/compartmentalization where H.sup.+ is higher.

[0226] Another example makes use of a plurality of probes. For example, sensor T may distribute according to temperature and sensor H may distribute in accordance with pH. Where concentrations of both are elevated they may interact for intended effect.

[0227] Other interactions of two or more sensor probes which attract active moieties to the intended target cell or zone of cells are possible. Active sensors or moieties may exert activity through binding an intended cell receptor, through enzymatic action, through scavenging substrate or metabolite, through inducing or inhibiting protein expression, though affecting intercellular binding, communication, through recruiting or activating natural body substances or components, etc.

[0228] Vesicles, sensitive to heat, pH, ROS or other chemical attractant or binding agent may serve as couriers for one or more effector molecules. Engineered viruses may be activated at the targeted site, for example through binding to one or more probes, and exert desired outcome(s). Carrier protein, lipids or carbohydrate molecules or combinations thereof may stabilize probe or effector molecules during transport and/or delivery.

[0229] A vesicle whose lysis is exacerbated by higher temperatures acidic conditions, or both, may serve to deliver membrane binding agents to areas of lysis. Such binding agents may be inhibitors or ligands for any one or more cell surface markers, e.g., a transport protein, a receptor protein, an adhesion protein, etc., but since their availability for these agents to bind would follow lysis of the temperature and/or pH sensitive vesicle, these agents would be restricted to acting in the relevant zones of pH and/or temperature and, perhaps in some embodiments, one or more additional hypermetabolic harbinger(s).

[0230] In the United States, the U.S. Food and Drug Administration (FDA) is responsible for the regulation of clinical trial research using investigational products, including gene therapies for cancer indications. The FDA also regulates devices and combinations of therapy tools, drugs and/or devices. The regulatory rules may change over product categories as we learn more of the science risks and costs. While the invention disclosure is valid for its teachings everywhere, in the absence of regulatory approval in the US or other relevant jurisdiction, the skilled artisan is advised to confirm approvals including waste disposals and the like in practicing this invention.

Example 1

[0231] A vesicle is created that distributes across a pH gradient. The excess time the vesicle resides at the lower pH increases its probability to decompose or release carried molecules. The rate of decomposition is sensitive to temperature resulting in a highly synergistic effect for delivering the effectors when both temperature and H.sup.+ are increased. An engineered viral particle or other vector transportable through circulation, including, but not limited to: exosomes and ectosomes, shed vesicles, microvesicles, etc., may deliver effector molecules or compounds and/or may serve as a signal to attract other vectors to the site.

Example 2

[0232] Probe T distributes according to temperature tending to bind lipid membranes as a function of a factor including, but not limited to: to fluidity, temperature dependent membrane protein access, intercellular access, etc. Probe H binds probe T only when probe T is protonated. Accordingly, at lower pH H-T binding is greatly increased. Stoichiometry may be 1:1 H:T or other relationship, e.g., 2:1,3:1,4:1, 3:2, 1:2, 2:3, 1:4, etc. Probe H or probe T or an activated chimer of the two may be activated to deliver metabolic modulation or other instruction or may serve as a binding agent for another effector agent.