Disclosed herein are methods and compositions for treating or preventing neuropathic pain in a subject, the method comprising administering to a subject a therapeutically effective amount of prolactin, or a functional variant thereof, wherein the functional variant comprises a peptide of formula (I) or a pharmaceutically acceptable salt thereof: R.sup.1-C-R-I-X.sub.1-X.sub.2-X.sub.3-X.sub.4-N-C-R.sup.2 (I) (SEQ ID NO:1) wherein X.sub.1 is an amino acid residue selected from isoleucine (I) and valine (V); X.sub.2 is an amino acid residue selected from histidine (H) and tyrosine (Y); X.sub.3 is an amino acid residue selected from aspartic acid (D) and asparagine (N); X.sub.4 is an amino acid Nresidue selected from asparagine (N) and serine (S); R.sup.1 is selected from the group consisting of YLKLLK, LKLLK, KLLK, LLK, LL, K or R.sup.1 is absent; and R.sup.2 is G (glycine), or R.sup.2 is absent.

The invention provides modified T-cell receptors referred to herein as dominant negative ligand-chimeric antigen receptors (DNL-CARS). The present invention also provides T-cells expressing DNL-CARs such T cells also referred to herein as DNL-CAR-expressing T cells or DNL-CAR T cells. Also provided are tagged-DNL/CAR-T systems that direct CAR-T cells to tumor cells previously complexed to the DNL-Tag fusion. Also provided are tagged-DNL-antigen fusion proteins wherein the antigen portion of the fusion proteins recruits the patient's own immune system to neutralize cells tagged with the tagged DNL portion of the fusion protein.

Lipidated neuropeptides PrRP31, PrRP20, containing C14 to C16 fatty acid, and their analogs, wherein a sequence of IRPVGRF-NH.sub.2 at the C-terminus is variable in the site of isoleucine, valine and phenylalanine; said fatty acid is bound in position 1 or 11 for PrRP31 or its analog and in position 1 or 7 for PrRP20 or its analog; the bond comprises an amide bond between an amino acid having at least one free NH.sub.2 group and a carboxylic group of the fatty acid and alternatively includes also a binding through arm X.sup.2, which is a hydrophilic linker selected from a group comprising -alanine, -aminobutyric acid or -glutamic acid; for use in the treatment and prevention of diseases, which are Alzheimer's disease (AD), Parkinson's disease (PD), cognitive impairment no dementia (CIND), brain trauma, and neurodegenerative changes and disorders.

Provided herein are immunomodulatory polypeptides containing first and second submits of a cytokine or a chemokine connected by a joining region containing a targeting moiety that binds to a target molecule. In some aspects, the disclosure further relates to engineered cells and compositions comprising the immunomodulatory polypeptides and methods for their administration to subjects. In some embodiments, the cells engineered to contain the immunomodulatory polypeptide, such as T cells, further contain a genetically engineered antigen receptor that specifically binds to antigens, such as a chimeric antigen receptor (CAR). In some embodiments, features of the polypeptides, engineered cells, and methods provide for improved treatment of diseases or disorders, such as by reducing adverse effects of cytokine or chemokine therapy, or increasing activity, efficacy and/or persistence or decreasing immunogenicity of adoptive cell therapy.

The invention is directed to compositions to screen for compounds, e.g., small molecules or drugs, that can modulate or inhibit enzymes, e.g., proteases, such as viral proteases, e.g., HIV proteases; and methods for making and using these compositions. In alternative embodiment, the invention provides compositions and methods for identifying compositions, e.g., drug molecules that can modulate or inhibit enzymes, e.g., proteases, proteinases or peptidases or the like, e.g., HIV proteases. In alternative embodiments, the invention provides cell-based assays to screen for compositions. e.g., small molecules or drugs, that modulate or inhibit or modify the activity of enzymes such as proteases, proteinases or peptidases or the like, such as calcium-dependent protein convertases involved in HIV envelop protein processing, including cleavage of the HIV gp160 envelope precursor, resulting in gp120 and gp41 envelope products. In alternative embodiment, the compositions and methods of the invention are adapted for high through-put or multiplexed screening of compounds, e.g., drug molecules that can modulate or inhibit enzymes.

The disclosure provides a reversal group of biomarkers comprising a reversal pair and a reversal triplet, wherein the reversal pair and reversal triplet exhibit a change in reversal value between pregnant females at risk for pre-term birth and term controls. Also provided is a method of determining probability for preterm birth in a pregnant female, the method comprising measuring in a biological sample obtained from the pregnant female, a reversal value for a reversal pair and a reversal triplet to determining the probability of preterm birth in the pregnant female.

Provided herein are methods of treating prolactin receptor positive breast cancer using an antibody drug conjugate (ADC) comprising an anti-PRLR antibody or antigen-binding fragment thereof conjugated to a cytotoxic agent. In certain embodiments, the anti-PRLR antibody or antigen-binding fragment thereof is conjugated to maytansinoid. In certain embodiments, the method of treating PRLR positive breast cancer includes administering the ADC in combination with one or more chemotherapeutic agents.

The present disclosure provides antagonist fusion polypeptides (e.g., with extended half-life, improved antagonist activity) comprising (i) a serum albumin binding polypeptide; (ii) a polypeptide hormone analog capable of antagonizing its receptor activation; and (iii) a linker, as well as various related technologies including, methods of producing and using such fusion polypeptides.

The invention is directed to compositions to screen for compounds, e.g., small molecules or drugs, that can modulate or inhibit enzymes, e.g., proteases, such as viral proteases, e.g., HIV proteases; and methods for making and using these compositions. In alternative embodiment, the invention provides compositions and methods for identifying compositions, e.g., drug molecules that can modulate or inhibit enzymes, e.g., proteases, proteinases or peptidases or the like, e.g., HIV proteases. In alternative embodiments, the invention provides cell-based assays to screen for compositions, e.g., small molecules or drugs, that modulate or inhibit or modify the activity of enzymes such as proteases, proteinases or peptidases or the like, such as calcium-dependent protein convertases involved in HIV envelop protein processing, including cleavage of the HIV gp160 envelope precursor, resulting in gp120 and gp41 envelope products. In alternative embodiment, the compositions and methods of the invention are adapted for high through-put or multiplexed screening of compounds, e.g., drug molecules that can modulate or inhibit enzymes.

Lipidated neuropeptides based on PrRP31, PrRP20, containing C14 and/or C16 fatty acid, in which sequence of IRPVGRF-NH.sub.2 at the C-terminus is variable in the site of isoleucine, valine and phenylalanine; the fatty acid is bound in position 1 or 11 for PrRP31 or its analog and in position 1 or 7 for PrRP20 or its analog; the fatty acid is bound directly or through a hydrophilic linker X.sup.2, for use in the treatment and prevention of neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), cognitive impairment no dementia (CIND), brain trauma, and neurodegenerative changes and disorders.