US 20170172932A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2017/0172932 A1 Peyman (43) Pub. Date: Jun. 22, 2017 (54) EARLY CANCER DETECTION AND A 6LX 39/395 (2006.01) ENHANCED IMMUNOTHERAPY A61R 4I/00 (2006.01) (52) U.S. Cl. (71) Applicant: Gholam A. Peyman, Sun City, AZ CPC .......... A61K 9/50 (2013.01); A61K 39/39558 (US) (2013.01); A61K 4I/0052 (2013.01); A61 K 48/00 (2013.01); A61K 35/17 (2013.01); A61 K (72) Inventor: sham A. Peyman, Sun City, AZ 35/15 (2013.01); A61K 2035/124 (2013.01) (21) Appl. No.: 15/143,981 (57) ABSTRACT (22) Filed: May 2, 2016 A method of therapy for a tumor or other pathology by administering a combination of thermotherapy and immu Related U.S. Application Data notherapy optionally combined with gene delivery. The combination therapy beneficially treats the tumor and pre (63) Continuation-in-part of application No. 14/976,321, vents tumor recurrence, either locally or at a different site, by filed on Dec. 21, 2015. boosting the patient’s immune response both at the time or original therapy and/or for later therapy. With respect to Publication Classification gene delivery, the inventive method may be used in cancer (51) Int. Cl. therapy, but is not limited to such use; it will be appreciated A 6LX 9/50 (2006.01) that the inventive method may be used for gene delivery in A6 IK 35/5 (2006.01) general. The controlled and precise application of thermal A6 IK 4.8/00 (2006.01) energy enhances gene transfer to any cell, whether the cell A 6LX 35/7 (2006.01) is a neoplastic cell, a pre-neoplastic cell, or a normal cell. US 2017/0172932 A1 Jun. 22, 2017 EARLY CANCER DETECTION AND 0007. One embodiment is a method for evaluating treat ENHANCED IMMUNOTHERAPY ment outcome in a patient having a genetic predisposition for a malignant neoplasm before clinical manifestation of 0001. This application is a continuation-in part of co the neoplasm can be seen radiographically. The method pending application Ser. No. 14/976,321 filed Dec. 21, 2015 permits visualization of any tumor, whether located exter which is expressly incorporated by reference herein in its nally on a patient’s body or located internally in the body, entirety. and as Small as 2 mm in diameter, producing a biomarker, 0002 Various factors may lead one to suspect the pres either a biomarker specific for the tumor or a general ence of a small cancerous or neoplastic tumor in a patient. biomarker. Such factors include the patient's genetic history, environ 0008. In general, a biomarker indicates a disease process. mental conditions to which the patient is or has been As Subsequently described, a biomarker can be a protein, exposed, the presence of biomarkers in the patient’s blood, antigen, enzyme, hormone, carbohydrate, toxin, DNA, an or the presence of a lesion on a patient's skin or mucosal organism such as bacteria, tumor cell, exosome, or indirectly Surface. A small neoplasm, however, is often not recognized an antibody, present in a liquid biopsy specimen. It can be unless and until it produces some clinical symptom. produced by the plasma cells, against a tumor antigen, etc. 0003. In a patient having a genetic mutation indicating a 0009. The method uses antibodies conjugated with nano predisposition to cancer, prophylactic Surgical intervention, particles which include but are not limited to quantum dots, Such as a bilateral mastectomy performed in a patient having with the conjugated form collectively termed functionalized a genetic mutation indicating a predisposition to breast nanoparticles, that are heated under specified conditions to cancer, is seldom performed. Additionally, a genetic predis produce a photoacoustic signal that is then visualized to position to one type of cancer may not lead to that type of locate the tumor to which the nanoparticles are attached. cancer, e.g. breast cancer, but it may lead to another unsus Nanoparticles may be used for qualitative and quantitative pected type of cancer, e.g. malignant melanoma. Even if the assessment of an analyte in the blood or other tissue using other type of cancer is suspected, because of the finding of photoacoustic technology, U.S. Pat. No. 8,554.296. As pre biomarkers in the blood, a small internal lesion may not be viously stated, as used herein, unless specifically stated seen on radiography, or may not be accessible by Surgery, or otherwise, nanoparticles include but are not limited to quan the collateral complications may not be acceptable. It may tum dots. not suffice to just know the biomarker for a tumor, because 00.10 Early stage small neoplastic cells produce bio this information may not indicate whether the tumor is a markers that are either specific to the tumor cells or that primary site or a metastatic site, the tissue of its origin, represent the body's response to the tumor as an antibody. and/or its location. It is appreciated that some treatment The biomarkers can be proteomic, genetic, epigenetic or techniques such as Surgery or radiation may be useful, but glycomic biomolecules. These biomolecules can be recog only if the tumor is tissue specific. Radiation and chemo nized in the patient’s tissue samples or in the blood. Their therapy also have their own side effects, and may not destroy existence can be demonstrated thus far chemically using, the tumor completely. Larger tumors present a much com e.g., immunoassay or PCR methods. Quantitation of these plex problem, e.g., mutations in one area of the tumor are biomarkers is also important to determine disease progres usually different from mutations in another area of the same sion and prognosis of the disease. tumor. 0011 Biomarkers for many diseases are found in the 0004. It is clearly preferable, then, to manage small early blood. As Subsequently disclosed, biomarkers detected in a neoplasms that have not progressed to a larger tumor to liquid biopsy sample are used to generate antibodies against provide the patient an improved clinical prognosis. them using known methods in the art. The anti-tumor 0005. The invention includes a method of therapy for a antibodies are used to coat nanoparticles in the inventive non-Surgically accessible tumor by administering a combi method, where a lesion can be imaged regardless of the nation of thermotherapy and immunotherapy combined with lesion size or location in the body. The method is not limited gene delivery. The combination therapy beneficially treats to tumor detection and/or therapy. As only one example, the tumor and prevents tumor recurrence, either locally or at detecting an antibody against anti-beta-amyloid protein a different site, by boosting the patient’s immune response present in Alzheimer's disease in a liquid biopsy specimen, both at the time or original therapy and/or for later therapy the method renders the plaque visible with the nanoparticles as a “booster to the original therapy. With respect to gene and accessible to the inventive treatment. As another delivery, the inventive method may be used in cancer example, the method can also be used to detect and/or treat therapy, but is not limited to such use; it will be appreciated inflammatory processes, etc. that the inventive method may be used for gene delivery in 0012. The inventive method is applicable to any pro general. For example, the inventive method facilitates cel cesses or diseases that produce a biomarker detectable in a lular gene uptake by current methods that lack a thermal liquid biopsy specimen. It is applicable to a lesion including energy component, Such as electroporation, quantum dot an abscess, an ulcer, a tumor either benign or malignant, an delivery, etc. The controlled and precise application of ischemic area of a stroke and/or an area of the brain affected thermal energy enhances gene transfer to any cell, whether by a stroke whether visible or microscopically. the cell is a neoplastic cell, a pre-neoplastic cell, or a normal 0013 Well over a thousand proteins are differentially cell. expressed in human cancers and thus may serve as biomark 0006. The inventive method provides in vitro and in vivo ers. Such proteins play a role in cancer-related processes precision immunotherapy to decrease or eradicate a malig Such as angiogenesis, apoptosis, cell differentiation, cell nant neoplasm at an early stage of the disease. This method signaling, hematopoiesis, hormonal control, immune reac provides a vaccination effect to prevent at least the same tions, etc. Exemplary biomarkers include, but are not limited kind of cancer or recurrences. to, CEA for both malignant pleural effusion and peritoneal US 2017/0172932 A1 Jun. 22, 2017 cancer dissemination; HER-2/neu for stage IV breast cancer; endoscope and a cutting probe, has a fast post-operative bladder tumor antigen for urothelial cell carcinoma; thyro recovery. Such a method is in contrast to completely remov globulin for thyroid cancer metastasis; a-fetoprotein for ing the uterus with the tumor intact out of caution that the hepatocellular carcinoma; PSA for prostate cancer; CA 125 tumor may harbor neoplastic cells, but using a large incision for non-small cell lung cancer; CA 19.9 for pancreatic with significantly higher operative risks and post-operative cancer; CA 15.3 for breast cancer; the combination of leptin, complication probabilities. Another, more problematic prolactin, osteopontin, and IGF-II for ovarian cancer, the example, is the decision for a woman having genetic dis combination of CD98, fascin, spIgR, and 14-3-3 eta for lung position to breast cancer without any physical or radiologi cancer; troponin I for myocardial infarction, and B-type cal manifestation.