Provided are polynucleotides and viral vectors, particularly, alphavirus vectors such as Sindbis viral vectors, which encode multiple, e.g., two or more, epitopes of at least one tumor associated antigen in which each epitope is separated by a processing or enzyme cleavage site. The multiple epitopes of the two or more tumor associated antigens encoded by the described polynucleotides and viral vectors may be the same or different. Methods of treating mammalian subjects having a cancer or tumor expressing the tumor associated antigen epitopes are provided, in which the viral vectors encoding the multiple epitopes, as well as other immunostimulatory or immunomodulatory components, generate an anti-cancer or anti-tumor immune response in which high levels of effector T cells increase the survivability of tumored mammalian subjects and result in epitope spreading, thus providing a further enhancement of the immune response.

Certain universal neoepitopes and cancer specific neoepitopes and methods therefor are presented that may be used in immunotherapy and cancer diagnosis. Preferred therapeutic and diagnostic compositions include antibodies or fragments thereof that bind to neoepitopes on cancer cells.

Described herein is a method for cancer immunotherapy by administering to a subject an mRNA vaccine designed to express the carbonyl terminal segment of human chorionic gonadotropin (hCG). Also described an improved adjuvant by co-administration of an antisense IL-10 molecule to shift the vaccine immune response to enhanced T-cell responses to hCG. Other embodiments relate to devices and methods for improved delivery of the mRNA vaccine and adjuvant. The intended use involves repeated administration of the vaccine components to subjects over an interval of several months in a repeated boosting strategy.

Certain universal neoepitopes and cancer specific neoepitopes and methods therefore are presented that may be used in immunotherapy and cancer diagnosis. Preferred therapeutic and diagnostic compositions include antibodies or fragments thereof that bind to neoepitopes on cancer cells.

The present invention provides an agent for adjuvant therapy of tumors that exerts remarkable inhibitory effects on tumor metastasis and recurrence while developing few side effects. The agent for adjuvant therapy comprises, as an active ingredient, a peptide having 4 linked CTL epitopes.

The present application is directed to an anti-Adrenomedullin (ADM) antibody or anti-ADM antibody fragment or anti-ADM non-Ig scaffold for use in the treatment or prevention of shock in a patient, wherein said patient is characterized by having a level of dipeptidyl peptidase 3 (DPP3) in a sample of bodily fluid below a threshold and said anti-ADM antibody or anti-ADM fragment or anti-ADM non-Ig scaffold binds to the N-terminal part (amino acid 1-21) of ADM: YRQSMNNFQGLRSFGCRFGTC (SEQ ID No. 14).

A method for modulating the adrenomedullin (ADM) activity of a patient by administering to the patient an anti-adrenomedullin (ADM) antibody or an anti-adrenomedullin antibody fragment. The method may be used, for example, in therapy of a chronical or acute disease or acute condition of a patient for prevention or reduction of organ dysfunction or organ failure. In a preferred embodiment the method is for use in therapy of a chronical or acute disease or acute condition of a patient for prevention or reduction of kidney dysfunction or kidney failure or liver dysfunction or liver failure.

Disclosed herein are non-viral methods to ablate FOXP1 in T cells while effectively expressing chimeric receptors. Therefore, disclosed herein is a chimeric cell expressing a chimeric receptor, wherein the chimeric receptor is encoded by a transgene, and wherein the transgene is inserted in the genome of the cell at a location that disrupts expression or activity of an endogenous FOXP1 protein.

Disclosed herein are materials and methods for the treatment of stress-related disorders and cancer. The disclosure provides an antibody, or antigen binding fragment thereof, that specifically binds to a region of corticotropin-releasing hormone (CRH). The disclosure also provides methods of treating a disorder associated with HPA axis activation, such as a stress-related disorder or cancer, comprising administering to a subject in need thereof an antibody or antigen binding fragment thereof described herein in an amount effective to treat the disorder.

Described herein is a method of preventing or treating a disease in a mammalian subject, comprising administering to the subject who is in need thereof an effective dosage of a pharmaceutical composition comprising a virus like particle (VLP) comprising: an alphavirus replicon comprising a recombinant polynucleotide, wherein the polynucleotide comprises a sequence encoding both subunits of a human class II major histocompatibility antigen, a retroviral gag protein, and a fusogenic envelope protein, wherein the VLP does not contain an alphavirus structural protein gene.