Embodiments of the disclosure concern methods and compositions for immunotherapy for human papillomavirus infection and diseases associated therewith. In specific embodiments, methods concern production of immune cells that target one or more antigens of HPV16 and/or HPV18, including methods with stimulation steps that employ IL-7 and IL-15, but not IL-6 and/or IL-12. Other specific embodiments utilize stimulations in the presence of certain cells, such as costimulatory cells and certain antigen presenting cells.

The present invention relates to CTL peptide epitopes, high-throughput methods for their identification, and their uses. In particular, the present invention relates to peptide epitopes for cancer immunotherapy and Hepatitis C Virus vaccines. The present invention also relates to methods and systems for identifying antigen-specific CTLs.

In one embodiment, the present disclosure provides an engineered cell having a first chimeric antigen receptor polypeptide including a first antigen recognition domain, a first signal peptide, a first hinge region, a first transmembrane domain, a first co-stimulatory domain, and a first signaling domain; and a second chimeric antigen receptor polypeptide including a second antigen recognition domain, a second signal peptide, a second hinge region, a second transmembrane domain, a second co-stimulatory domain, and a second signaling domain; wherein the first antigen recognition domain is different than the second antigen recognition domain.

Embodiments of the disclosure encompass compositions comprising immune effector cells, such as natural killer (NK) cells, where the cells comprise one or more exogenously provided interleukins (IL), and wherein the cell optionally comprises one or more engineered receptors. In specific embodiments, the IL is not IL-15, and is IL-12, IL-21, or both. The NK cells may be utilized for treatment of cancer of any kind, including at least glioblastoma.

The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules.

Provided are methods and compositions directed to the treatment of an individual having cancer by (i) administering to the individual an adoptive cellular immunotherapy composition comprising CAR T cells and (ii) administering to the individual an interleukin-15 receptor agonist, such as, for example, a long-acting interleukin-15 receptor agonist.

A microparticle is described comprising an antigen and a costimulatory component derived from an antigen presenting cell. The microparticle may be used for stimulating T cells ex vivo, followed by administration to a subject, e.g., as part of a personalized, customized therapeutic treatment of cancer or a tumor, an autoimmune disease or an allergic reaction, hypersensitivity reaction, an infection or infectious disease, an injury or other damage, a transplant or other surgical site, or a blood clot. It may also be used for the controlled release of a cytokine for the regulation of immunity in general and for other therapeutic uses. Methods of treating a disease or medical condition in a subject by exposing leukocytes from the subject to the microparticle, then reinfusing the leukocytes into the subject are provided. Methods of preparing an activated cytotoxic T cell population specific for an antigen are also provided.

Chimeric antigen receptors (CARs) with binding domains derived from a novel suite of CD33-binding antibodies are described. The CARs include optimized short and intermediate spacer regions. The current disclosure also provides methods of cell expansion/activation processes utilizing IL-2, IL-7, IL-15, and/or IL-21 that improve cellular proliferation and cell lysis of the CARs as described.

Provided herein are CAR-T compositions that are directed to GPC3, including a chimeric receptor, and engineered immune cells to GPC3. The disclosure also provides vectors, compositions, and methods of treatment using GPC3 antigen binding molecules and engineered immune cells, optionally in combination with expression of IL-18. GPC3 CAR compositions provided herein can be used for the treatment of certain cancers.

The present disclosure relates to methods and agents for antigen vaccination and inducing effective antigen-specific immune effector cell responses such as T cell responses. Specifically, the present disclosure relates to methods comprising administering to a subject (i) non-immunogenic RNA encoding a peptide or protein comprising an epitope for inducing an immune response against an antigen in the subject, i.e., non-immunogenic RNA encoding vaccine antigen; and (ii) an immunostimulant or RNA encoding an immunostimulant. Administering to the subject non-immunogenic RNA encoding vaccine antigen may provide (following expression of the RNA by appropriate target cells) vaccine antigen for stimulation, priming and/or expansion of immune effector cells and, thus, may induce an immune response against vaccine antigen (and disease-associated antigen) in the subject.