Wisconsin Alumni Research Foundation

University of Minnesota

Paul M Sondel

Zachary Scott Morris

Jamey Paul Weichert

Anatoly Pinchuk

Mario Otto

Bryan P Bednarz

Peter Carlson

Ravi Bhasker Patel

Shaoqin Gong

Augusto C Ochoa

Joseph J Grudzinski

Reinier Hernandez

Mingzhou Ye

Fritz H Bach

Michael J Sheehy

Marilyn L Bach

Barbara Alter

Rudolf Wank

Jamie Weichert

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

Provided herein are nanoparticles comprising a polyplex core comprising one or more pH-responsive polymers and one or more anionic immune adjuvants, wherein each pH-responsive polymer comprises ionizable amine groups; and a shell of bacterial cell membrane components at least partially coating the polyplex core, wherein the bacterial cell membrane components comprise TLR 2 and/or TLR 4 agonists. Also provided are methods of stimulating an immune response in a mammal using the nanoparticle.

Bacterial membrane nanoparticles as an immunotherapy system for cancer treatment

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).

In accordance with the present invention, a method of culturing lymphocytes is disclosed in which the lymphocytes are cultured in the presence of interleukin-2 (IL-2) and an antibody to a lymphocyte surface receptor, preferably an antibody to a lymphocyte T3 surface receptor. Preferably, the antibody is monoclonal. Cells cultured with anti-CD3 maintain their LAK activity as they increase in number. The cells can also be cultured in the presence of an additional lymphokine to obtain additional LAK activity. Methods of medical treatment are also disclosed in which cells cultured in accordance with the culturing methods of the present invention are introduced into the individual to be treated.

Method of culturing lymphocytes and method of treatment using such

A cellular method for typing lymphocyte defined human leukocyte antigens by utilizing human blood leukocytes which have been sensitized to proliferatively respond to the secondary stimulus of the leukocyte antigens to which they have been sensitized. The sensitization is accomplished by incubating, in vitro, in a mixed leukocyte culture, the leukocytes to be sensitized with leukocytes differing by only a single major histocompatibility complex haplotype or a single HLA-D antigenic determinant.

Growing community of inventors

Madison, WI, United States of America

Paul M Sondel