The present invention relates to peptides, nucleic acids, and cells for use in the immunotherapy of cancer. The present invention furthermore relates to survivin-derived tumor-associated cytotoxic T cell (CTL) peptide epitopes, alone or in combination with other tumor-associated peptides that serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses. The present invention specifically relates to three novel peptide sequences and variants thereof derived from HLA class I and class II molecules of human tumor cells that can be used in vaccine compositions for eliciting anti-tumor immune responses.

Provided herein are cancer stem cell targeted cancer vaccines and methods for treating and vaccinating against cancer. Also contained herein are regimens by which cancer stem cell targeted cancer vaccines are administered, such regimens comprising peptides, compositions, immunomodulatory agents, and emulsifiers. Also provided are the patient populations to which the regimens are to be administered, and the dosages, schedules, and route of administration for the regimens.

Provided is a method for evaluating the progression of glioma in an individual comprising monitoring the levels of circulating exosomes that are positive for survivin and a glial marker (such as glial fibrillary acidic protein). An increase in the level of such exosomes is indicative of poor prognosis. Levels of circulating exosomes that are positive for survivin and glial marker can also be used for evaluating the efficacy of a therapy for glioma in an individual, and modifying the therapy or introducing additional therapy if levels of such exosomes are found to be increasing.

Provided is a pharmaceutical composition, including an antigen fusion protein which includes an antigen and an antagonist of an Fc gamma receptor. Also provided is a method of enhancing immunogenicity of an antigen, including conjugating the antigen with an antagonist of an Fc gamma receptor to form an antigen fusion protein. Also provided is a method of enhancing an immune response to an antigen in a subject, including administering to the subject an effective amount of an antigen fusion protein which includes an antigen and an antagonist of an Fc gamma receptor. The present invention may be applied in the development of potent vaccines based on targeting vaccine antigens to antigen-presenting cells via binding to Fc gamma receptors.

Provided herein are recombinant fusion polypeptides comprising one or more antigenic peptides (e.g., fused to a PEST-containing peptide) from cancer-associated proteins. The antigenic peptides can comprise one or more or all of an antigenic peptide comprising a recurrent cancer mutation, an antigenic peptide comprising a heteroclitic mutation, or an antigenic peptide fused to a ubiquitin protein. For example, provided herein are recombinant fusion polypeptides comprising two or more antigenic peptides (e.g., fused to a PEST-containing peptide), wherein each antigenic peptide comprises a recurrent cancer mutation, and wherein at least two of the antigenic peptides are fragments of the same cancer-associated protein. Also provided are nucleic acids encoding such fusion polypeptides, recombinant bacteria or Listeria strains comprising such fusion polypeptides or such nucleic acids, and cell banks comprising such recombinant bacteria or Listeria strains. Also provided herein are methods of generating such fusion polypeptides, such nucleic acids, and such recombinant bacteria or Listeria strains. Also provided are immunogenic compositions, pharmaceutical compositions, and vaccines comprising such fusion polypeptides, such nucleic acids, or such recombinant bacteria or Listeria strains. Also provided are methods of inducing an anti-tumor-associated-antigen immune response in a subject, methods of inducing an anti-tumor or anti-cancer immune response in a subject, methods of treating a tumor or cancer in a subject, methods of preventing a tumor or cancer in a subject, and methods of protecting a subject against a tumor or cancer using such recombinant fusion polypeptides, nucleic acids, recombinant bacteria or Listeria strains, immunogenic compositions, pharmaceutical compositions, or vaccines.

The present invention relates to peptides, nucleic acids, and cells for use in the immunotherapy of cancer. The present invention furthermore relates to survivin-derived tumor-associated cytotoxic T cell (CTL) peptide epitopes, alone or in combination with other tumor-associated peptides that serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses. The present invention specifically relates to three novel peptide sequences and variants thereof derived from HLA class I and class II molecules of human tumor cells that can be used in vaccine compositions for eliciting anti-tumor immune responses.

Provided herein are methods, compositions and uses involving immunotherapies, such as adoptive cell therapy, e.g., T cell therapy, and inhibitors of a TEK family kinase, such as BTK or ITK. The provided methods, compositions and uses include those for combination therapies involving the administration or use of one or more such inhibitor in conjunction with another agent, such as an immunotherapeutic agent targeting T cells, such as a therapeutic antibody, e.g., a multispecific (e.g., T cell engaging) antibody, and/or genetically engineered T cells, such as chimeric antigen receptor (CAR)-expressing T cells. Also provided are methods of manufacturing engineered T cells, compositions, methods of administration to subjects, nucleic acids, articles of manufacture and kits for use in the methods. In some aspects, features of the methods and cells provide for increased or improved activity, efficacy, persistence, expansion and/or proliferation of T cells for adoptive cell therapy or endogenous T cells recruited by immunotherapeutic agents.

A method of treating cancer comprising and reducing autoimmune side effects in administration of anti-CTLA-4 antibodies. The invention provides methods for low dose immune checkpoint (IC) treatment of metastatic cancer by delivering anti-CTLA-4 and anti-PD-1 antibodies to cancer patients. Methods also provide for IL-2 stimulation for the activation of T cells against tumor cells. The invention further provides methods for daily cyclic high fever response (hyperthermia) during IL-2 therapy. The methods provide treatment of metastatic cancer without unacceptable autoimmune side effects.

A PD-1 antibody or a functional fragment thereof, and use of said antibody in the preparation of a medicament for treating tumors are provided.

Compositions of multipeptide vaccines comprising at least seven tumor associated antigens, compositions of antigen presenting cell (e.g., dendritic cell) based vaccines presenting epitopes from at least seven tumor associated antigens, and methods of making same, are provided herein. Also, disclosed are methods for treating gynecological and peritoneal cancers using such vaccines.