The present invention provides methods compositions and methods of preparing autologous (or allogeneic) B cells that secrete a therapeutic monoclonal antibody of interest or B cells with an altered function.

This disclosure relates to methods and agents for modulating adoptive immunotherapy to enable bioengineered immune cells to utilize xenobiotic fuel, e.g., in a low glucose environment. The immune cells may be used, e.g., for treatment of a tumor or cancer, such as part of a therapeutic treatment of cancer or for treatment of a bacterial, fungal, or viral infection, alone or in combination with a low glucose (e.g., ketogenic) diet. They may also be used to treat a tumor, a cancer, an infection, an autoimmune disease, or an inflammatory or neuroinflammatory disease or condition in a patient on a low glucose diet. The immune cells may be used in combination with a scaffold or platform or with a microparticle or nanoparticle for localization of treatment or xenobiotic nutrients or for controlled release, as well as for other therapeutic uses.

In one aspect, disclosed herein are methods of expanding tumor infiltrating lymphocytes (TILs) in vitro or ex vivo comprising obtaining TILs and culturing the TILs in media comprising one or more CD40 agonists (such as, for example, a CD40 ligand (CD40L) and/or anti-CD40 antibody).

The various embodiments of the disclosure relate generally to processes, methods, and systems for generating functional B cells ex vivo. It is particularly useful for ex vivo generation of antigen-specific germinal-center (GC) like B cells that are capable of efficient B cell expansion, immunoglobulin (Ig) class switching/class switching recombination (CSR), expression of germinal B cell phenotypes, antibody secretion, and somatic hypermutation (SHM) and resulting affinity maturation center phenotypes.

This invention provides novel carbonic anhydrase (CAIX) nucleic acid and peptide sequences, as well as related methods and compositions, including anti-cancer immunogenic agent(s) (e.g. vaccines and chimeric molecules) that elicit an immune response specifically directed against cancer cells expressing a CAIX antigenic marker. The novel CAIX variant and related compositions are useful in a wide variety of treatment modalities including, but not limited to protein vaccination, DNA vaccination, and adoptive immunotherapy.

Disclosed herein are methods and platforms for increasing utility and efficacy of a cellular vaccine. Specifically, disclosed are steps that optimize ex vivo B cell expansion and boost host in vivo immunity. Also disclosed is a platform for enhancing effectiveness of antigen presentation and antigen-specific immune responses. Also disclosed is a method for enhancing effectiveness of APCs in a subject. Also disclosed are vaccines and kits based on the platform.

Provided by the disclosure are methods for modulating differentiation of regulatory T cells (e.g., CD4.sup.+ or CD8.sup.+ regulatory T cells). In some embodiments, methods include contacting regulatory T cells with an agent that decreases Helios activity and/or Helios expression.

Methods for diagnosing and prognosing autoimmune diseases and T cell lymphomas are provided, for example by measuring levels of intracellular osteopontin (OPN-i). Also provided are screening methods for identifying activators and inhibitors of the transcription factor Bcl6, which is involved in T cell activation/differentiation. Other aspects of the disclosure provide methods for enhancing adoptive T cell transfer.

The chimeric antigen receptor that recognizes CCR8 as an antigen of the present invention has cytotoxic activity against CCR8-expressing cells by being expressed in effector cells.

The present disclosure relates to targeted degradation platform technology. For example, the present disclosure relates to bispecific binding agents for degrading endogenous proteins, whether membrane-associated or soluble, using the lysosome pathway. The disclosure also provides methods useful for producing such agents, nucleic acids encoding same, host cells genetically modified with the nucleic acids, as well as methods for modulating an activity of a cell and/or for the treatment of various disorders.