Wisconsin Alumni Research Foundation

Cellectar, Inc.

University of Michigan

Cellectar Biosciences, Inc.

The Board of Regents Acting for and on Behalf of the University of

Jamey Paul Weichert

Anatoly Pinchuk

Marc Longino

Raymond E Counsell

Marc A Longino

Chorom Pak

Mario Otto

Joseph J Grudzinski

Paul M Sondel

Zachary Scott Morris

William R Clarke

Bryan P Bednarz

Kevin Kozak

Benjamin Titz

Irawati Kandela

Nathan Stehle

Peter Carlson

Wolfgang A Tome

Susan P Schwendner

Douglas A Bakan

Mark A Rampy

Reinier Hernandez

Anatoly N Pinchuk

Robert Jeraj

Douglas Anthony Bakan

Wolfgang Axel Tomé

Ravi Bhasker Patel

Fotis Asimakopoulos

Roberta Marino

Kevin R Kozak

Dana C Baiu

Sharon Weber

Joseph O Nwankwo

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: wherein Ris a radioactive halogen isotope, n is 18 and Ris —N(CH).

Radiohalogenated agents 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: wherein Rcomprises 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 Ris &#x2014;N(CH).

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 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: wherein Rcomprises 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 Rcomprises a radioactive halogen isotope. In one such embodiment, a is 1, n is 18, m is 0, b is 1, and Ris &#x2014;N(CH).

Using targeted radiotherapy (TRT) to drive anti-tumor immune response to immunotherapies

Alkylphosphocholine analogs incorporating a chelating moiety that is chelated to gadolinium are disclosed herein. The alkylphophocholine analogs are compounds having the formula: or a salt therof. Rincludes a chelating agent that is chelated to a gadolinium atom; a is 0 or 1; n is an integer from 12 to 30; m is 0 or 1; Y is &#x2014;H, &#x2014;OH, &#x2014;COOH, &#x2014;COOX, &#x2014;OCOX, or &#x2014;OX, wherein X is an alkyl or an arylalkyl; Ris &#x2014;NH, &#x2014;NHZ, &#x2014;NHZ, or &#x2014;NZ, wherein each Z is independently an alkyl or an aroalkyl; and b is 1 or 2. The compounds can be used to detect solid tumors or to treat solid tumors. In detection/imaging applications, the gadolinium emits signals that are detectable using magnetic resonance imaging. In therapeutic treatment, the gadolinium emits tumor-targeting charged particles when exposed to epithermal neutrons.

Long-lived gadolinium based tumor targeted imaging and therapy agents

The present invention is directed to a method of identifying, isolating, and enabling downstream analysis of circulating tumor cells comprising contacting a blood or blood serum sample of a subject with a composition comprising a phospholipid ether analog bound to a luminescent molecule or a magnetic bead and subjecting the blood or blood serum sample of the subject to fluorescent microscopy, flow cytometry or magnetic isolation.

Luminescent phospholipid analogs for the identification and isolation of circulating tumor cells

The present invention is directed to therapeutic compounds capable of targeting cancer cells and cancer stem cells. The present invention is further directed to compositions comprising these therapeutic compounds and methods of treating cancer comprising administering these therapeutic compounds.

Phospholipid ether analogs as cancer-targeting drug vehicles

Alkylphosphocholine analogs incorporating a chelating moiety that chelates a radioactive metal isotope are disclosed herein. The alkylphophocholine analogs, which can be used to treat or detect solid tumors, have the formula: Rincludes a chelating agent that is chelated to a metal atom, wherein the metal atom is a positron or single photon emitting metal isotope with a half life of greater than or equal to 4 hours, or an alpha, beta or Auger emitting metal isotope with a half life of greater than 6 hours and less than 30 days; a is 0 or 1; n is an integer from 12 to 30; m is 0 or 1; Y is &#x2014;H, &#x2014;OH, &#x2014;COOH, &#x2014;COOX, &#x2014;OCOX, or &#x2014;OX, wherein X is an alkyl or an arylalkyl; Ris &#x2014;NH, &#x2014;NHZ, &#x2014;NHZ, or &#x2014;NZ, wherein each Z is independently an alkyl or an aroalkyl; and b is 1 or 2.

Radioactive phospholipid metal chelates for cancer imaging and therapy

It is disclosed herein that that certain alkylphosphocholine analogs are preferentially taken up by malignant pediatric tumor cells. The alkylphophocholine analogs are compounds having the formula: or salts thereof, wherein n is an integer from 12 to 24; and Ris &#x2014;N(CH). The compounds can be used to treat pediatric solid tumors or to detect pediatric solid tumors. In therapeutic treatment, Rincludes a radioactive iodine isotope that locally delivers therapeutic dosages of radiation to the malignant pediatric tumor cells that preferentially take up the compound. In detection/imaging applications, Rincludes a detection moiety, such as a fluorophore or a radioactive iodine isotope.

Phospholipid ether analogs for imaging and targeted treatment of pediatric solid tumors

Alkylphosphocholine analogs incorporating a chelating moiety that is chelated to gadolinium are disclosed herein. The alkylphophocholine analogs are compounds having the formula: or a salt thereof. Rincludes a chelating agent that is chelated to a gadolinium atom; a is 0 or 1; n is an integer from 12 to 30; m is 0 or 1; Y is &#x2014;H, &#x2014;OH, &#x2014;COOH, &#x2014;COOX, &#x2014;OCOX, or &#x2014;OX, wherein X is an alkyl or an arylalkyl; Ris &#x2014;NH, &#x2014;NHZ, &#x2014;NHZ, or &#x2014;NZ, wherein each Z is independently an alkyl or an aroalkyl; and b is 1 or 2. The compounds can be used to detect solid tumors or to treat solid tumors. In detection/imaging applications, the gadolinium emits signals that are detectable using magnetic resonance imaging. In therapeutic treatment, the gadolinium emits tumor-targeting charged particles when exposed to epithermal neutrons.

Long-lived gadolinium based tumor targeting imaging and therapy agents

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: wherein Ris a radioactive halogen isotope, n isand Ris &#x2014;N(CH).

Methods and compositions utilizing ether and alkyl phospholipid ether analog compounds for treating cancer and imaging, monitoring, and detecting cancer stem cells in humans.

Ether and alkyl phospholipid compounds for treating cancer and imaging and detection of cancer

A treatment schedule for radiopharmaceuticals is developed by collecting a volumetric history of tissue uptake in identified volumes of interest using emitted-radiation scans and relating this data to a treatment-radiopharmaceutical to develop a quantitatively accurate radiation treatment schedule of delivery amounts and delivery times of the treatment-radiopharmaceutical. This data may also be used to model biological effective dose and to prepare augmenting external radiation beam treatment schedules.

Treatment planning system for radiopharmaceuticals

It is disclosed herein that that certain alkylphosphocholine analogs are preferentially taken up by multiple myeloma tumor cells. The alkylphophocholine analogs are compounds having the formula: or salts thereof, wherein n is an integer from 12 to 24; and Ris &#x2014;NH, &#x2014;NHX, &#x2014;NHX, or &#x2014;NHX, wherein each X is independently &#x2014;CHor &#x2014;CH. The compounds can be used to treat multiple myeloma or to detect multiple myeloma. In therapeutic treatment, Rincludes a radionuclide that locally delivers therapeutic dosages of radiation to the multiple myeloma tumors cells that preferentially take up the compound. In detection/imaging applications, Rincludes a detection moiety, such as a fluorophore or a radiolabel.

Growing community of inventors

Fitchburg, WI, United States of America

Jamey Paul Weichert