A61K51/0408

TARGETED RADIOTHERAPY CHELATES FOR IN SITU IMMUNE MODULATED CANCER VACCINATION

The disclosed method of treating a malignant solid tumor in a subject includes the steps of administering to the subject an immunomodulatory dose of a radioactive phospholipid metal chelate compound that is differentially retained within malignant solid tumor tissue, and performing in situ tumor vaccination in the subject by introducing into at least one of the malignant solid tumors one or more agents capable of stimulating specific immune cells within the tumor microenvironment, or by performing another method of in situ tumor vaccination. In a non-limiting example, the radioactive phospholipid metal chelate compound has the formula:

##STR00001##

wherein R.sub.1 comprises a chelating agent that is chelated to a metal atom, wherein the metal atom is an alpha, beta or Auger emitting metal isotope with a half life of greater than 6 hours and less than 30 days. In one such embodiment, a is 1, n is 18, m is 0, b is 1, and R.sub.2 is N.sup.+(CH.sub.3).sub.3.

Radiohalogenated Agents for in Situ Immune Modulated Cancer Vaccination

A method of treating a malignant solid tumor in a subject is disclosed herein. The method includes the steps of administering to the subject an immunomodulatory dose of a radiohalogenated compound that is differentially taken up by and retained within malignant solid tumor tissue, and performing in situ tumor vaccination in the subject by intratumorally injecting into (or treating via a separate method) at least one of the malignant solid tumors a composition that includes one or more agents capable of stimulating specific immune cells within the tumor microenvironment. In certain exemplary embodiments, the radiohalogenated compound has the formula:

##STR00001##

wherein R.sub.1 is a radioactive halogen isotope, n is 18 and R.sub.2 is N.sup.+(CH.sub.3).sub.3.

In vivo methods of monitoring biodistribution

Non-invasive method of monitoring by radioactivity bioscanning the distribution of a biological entity in a subject in vivo by administering to the subject a radioiodinated form of the biological entity. The radioiodinated form is prepared by contacting an aqueous suspension of the biological entity with a radioiodinated construct of the structure F-S-L where F comprises a radioiodinated tyrosine moiety, S is a spacer covalently linking F to L, and L is a lipid.

GADOLINIUM EXPRESSED LIPID NANOPARTICLES FOR MAGNETIC RESONANCE IMAGING

Lipid nanoparticles expressing metal ions and methods for using the compositions for magnetic resonance imaging.

Radiohalogenated Agents for in Situ Immune Modulated Cancer Vaccination

A method of treating a malignant solid tumor in a subject is disclosed herein. The method includes the steps of administering to the subject an immunomodulatory dose of a radiohalogenated compound that is differentially taken up by and retained within malignant solid tumor tissue, and performing in situ tumor vaccination in the subject by intratumorally injecting into (or treating via a separate method) at least one of the malignant solid tumors a composition that includes one or more agents capable of stimulating specific immune cells within the tumor microenvironment. In certain exemplary embodiments, the radiohalogenated compound has the formula:

##STR00001##

wherein R.sub.1 is a radioactive halogen isotope, n is 18 and R.sub.2 is N.sup.+(CH.sub.3).sub.3.

Phospholipid ether analogs as agents for detecting and locating cancer, and methods thereof

The present invention provides methods for treating, detecting and locating recurrence of cancer, radiation and chemo insensitive cancer or metastasis of cancer selected from the group consisting of Lung cancer, Adrenal cancer, Melanoma, Colon cancer, Colorectal cancer, Ovarian cancer, Prostate cancer, Liver cancer, Subcutaneous cancer, Squamous cell cancer, Intestinal cancer, Hepatocellular carcinoma, Retinoblastoma, Cervical cancer, Glioma, Breast cancer and Pancreatic cancer in subject using phospholipid ether analogs.

Phospholipid analogs as diapeutic agents and methods thereof

The present invention provides methods and uses of phospholipid ether analogs as diagnostic and therapeutic agents for numerous cancers.

TREATMENT OF CANCERS WITH A REGIMEN OF TARGETED RADIONUCLIDE THERAPY AND DUAL CAR T CELL THERAPY

Described herein are genetically modified bispecific immune cells such as bicistronic and bivalent immune cells. The bispecific immune cells include an antigen recognition domain that specifically binds a tumor-specific antigen and an antigen recognition domain that specifically binds a radiation-induced cell surface marker. Also described are methods of treating cancer in a subject including administering to the subject a dose of a targeted radionuclide therapy (TRT) agent, and administering to the subject the genetically modified bispecific immune cell.

Using Targeted Radiotherapy (TRT) to Drive Anti-Tumor Immune Response to Immunotherapies

The disclosed method of treating a malignant solid tumor in a subject includes the steps of administering to the subject an immunomodulatory dose of a radioactive phospholipid ether metal chelate, a radiohalogenated phospholipid ether, or other targeted radiotherapy (TRT) agent that is differentially retained within malignant solid tumor tissue, and either (a) performing in situ tumor vaccination in the subject by introducing into at least one of the malignant solid tumors one or more agents capable of stimulating specific immune cells within the tumor microenvironment, or (b) performing immunotherapy in the subject by systemically administering to the subject an immunostimulatory agent, such as an immune checkpoint inhibitor. In a non-limiting example, the radioactive phospholipid ether metal chelate or radiohalogenated phospholipid ether has the formula:

##STR00001##

wherein R1 comprises a chelating agent that is chelated to a metal atom, wherein the metal atom is an alpha, beta or Auger emitting metal isotope with a half-life of greater than 6 hours and less than 30 days, or wherein R1 comprises a radioactive halogen isotope. In one such embodiment, a is 1, n is 18, m is 0, b is 1, and R2 is N+(CH3)3.

Glutaminase inhibitor therapy

Disclosed herein are methods of treating a tumor or cancer in a subject whose tumor or cancer cells express low levels of asparagine synthetase (ASNS), and compounds and compositions useful in such treatment. Also disclosed herein are methods of evaluating whether to administer a compound that inhibits glutathione production or a glutaminase inhibitor to a subject with a tumor or cancer.