The present invention is situated in the field of multimers used for targeted therapies. More particularly, the invention relates to methods for preparing multifunctional heteromultimeric protein complexes with a defined ratio of functional components and to multifunctional heteromultimeric protein complexes for directing complement-dependent cytolysis, optionally comprising a scaffold, which display three or more different functional components present in a defined relative ratio, of which one is a tracking component.

The present invention is situated in the field of multimers used for targeted therapies. More particularly, the invention relates to methods for preparing multifunctional heteromultimeric protein complexes with a defined ratio of functional components and to multifunctional heteromultimeric protein complexes for directing complement-dependent cytolysis, optionally comprising a scaffold, which display three or more different functional components present in a defined relative ratio, of which one is a tracking component.

Provided are compositions for increasing the half-life of a polypeptide or polypeptides in a canine and methods of their use. The compositions involve variant canine IgG Fc regions.

Provided are compositions for increasing the half-life of a polypeptide or polypeptides in a canine and methods of their use. The compositions involve variant canine IgG Fc regions.

The invention provides a polynucleotide including at least one of (a) a sequence encoding a fusion protein including an antigen-presenting MHC molecule capable of being presented extramembranously of an extracellular vesicle; (b) a sequence encoding a fusion protein including a T cell stimulating cytokine or a subunit thereof capable of being presented extramembranously of an extracellular vesicle; (c) a sequence encoding a fusion protein including a T cell co-stimulatory molecule capable of being presented extramembranously of an extracellular vesicle; (d) a sequence encoding a fusion protein including an antigen-presenting MHC molecule and a T cell stimulating cytokine or a subunit thereof capable of being presented extramembranously of an extracellular vesicle; and (e) a sequence encoding a fusion protein including an antigen-presenting MHC molecule, a T cell stimulating cytokine or a subunit thereof, and a T cell co-stimulatory molecule capable of being presented extramembranously of an extracellular vesicle.

The invention relates to plasmids capable of expressing a protein targeting immune cells when transformed into a lactic acid bacterial cell, wherein the protein is chosen from the group consisting of murine and human CXCL12 1α; CXCL17 and Ym1. The invention further relates to lactic acid bacteria transformed with a said plasmid, as well as the use of said lactic acid bacteria for wound healing in humans and animals.

Genetically programmed microorganisms, such as bacteria or virus, pharmaceutical compositions thereof, and methods of modulating and treating cancers are disclosed.

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 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, or wherein R.sub.1 comprises a radioactive halogen isotope. 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.

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 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, or wherein R.sub.1 comprises a radioactive halogen isotope. 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.

In certain embodiments, the present invention provides a musclin peptide and methods of increasing muscle growth, performance, resistance to injury and/or preventing or reducing muscle atrophy and improving overall skeletal muscle, metabolic and cardiac health in an animal in need thereof by administering a musclin peptide.