The present disclosure relates to compositions and methods of treating a subject having digestive tract cancer, the method comprising: administering an effective amount of a composition to the subject, the composition comprising a first population of cells comprising a first CAR binding a first antigen, and a second population of cells comprising a second CAR binding GCC, wherein the first antigen comprises a cell surface molecule of a white blood cell (WBC).

Methods of using polypeptides to modulate transforming growth factor-? (TGF?) signaling (e.g., TGF? receptors, antibodies or antigen-binding fragments thereof that specifically bind TGF? or a TGF? receptor) are provided. Compositions comprising the antibodies or fragments thereof and methods of using the same for treatment of diseases involving TGF? activity are provided. Nucleic acids, recombinant expression vectors, host cells, antigen binding fragments, and pharmaceutical compositions comprising these antigen binding agents and fragments thereof are also disclosed. The invention also provides therapeutic methods for utilizing the TGF? signaling modulators are provided herein.

Methods of using polypeptides to modulate transforming growth factor-? (TGF?) signaling (e.g., TGF? receptors, antibodies or antigen-binding fragments thereof that specifically bind TGF? or a TGF? receptor) are provided. Compositions comprising the antibodies or fragments thereof and methods of using the same for treatment of diseases involving TGF? activity are provided. Nucleic acids, recombinant expression vectors, host cells, antigen binding fragments, and pharmaceutical compositions comprising these antigen binding agents and fragments thereof are also disclosed. The invention also provides therapeutic methods for utilizing the TGF? signaling modulators are provided herein.

GUCY2C T cell antigen coupler (TAC) polypeptides having (i) an antigen-binding domain that binds GUCY2C, (ii) an antigen-binding domain that binds a protein associated with a TCR complex, and (iii) a T cell receptor signaling domain polypeptide are provided.

Isolated pluralities of T cells which recognize at least one epitope of an intestinal cancer antigen or CNS cancer antigen and pharmaceutical compositions comprising the same are disclosed. Methods of making a plurality of T cells that recognize at least one epitope of an intestinal cancer antigen or CNS cancer antigen are also disclosed. Methods of treating an individual who has been diagnosed with cancer of a mucosal tissue or preventing such cancer in an individual at elevated risk are disclosed as are nucleic acid molecules that comprise a nucleotide sequence that encode proteins that recognize at least one epitope of an intestinal cancer antigen or CNS cancer antigen and T cells comprising such nucleic acid molecules.

Embodiments relate to a modified cell comprising a polynucleotide encoding an antigen binding molecule and a polynucleotide encoding an agent targeting one or more extracellular matrix (ECM) molecules. In embodiments, the polynucleotide encoding the agent comprises at least a nucleic acid encoding Cathepsin K (CK), a nucleic acid encoding Neutrophil Elastase (NE), or a nucleic acid encoding MMP7. In embodiments, the nucleic acid encoding NE comprises a nucleic acid encoding NE and a nucleic acid encoding a signaling domain of IL2. In embodiments, expression of the polynucleotide encoding the agent is regulated by hypoxia-inducible factor 1-alpha (HIF1?), nuclear factor of activated T-cells (NFAT), forkhead box P3 (FOXP3), or nuclear factor kappa B (NF-?B).

The present disclosure relates to a soluble CD52 glycoprotein and its use in treating diseases regulated by effector T-cells, for example autoimmune diseases such as type 1 diabetes. The present disclosure also relates to fusion proteins comprising the soluble glycoprotein, to cells expressing high levels of CD52, and to diagnostic methods based on the detection of CD52 expression levels in a subject.

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.

Provided herein are antibodies and chimeric priming receptors that bind PSMA and antibodies and chimeric antigen receptors that bind CA9. Also provided are systems of chimeric priming receptors that bind PSMA and chimeric antigen receptors that bind CA9, cells expressing such systems, and methods of use thereof.

A chimeric antigen receptor (CAR), a cell (particularly an immune cell such as a regulatory T cell) expressing said CAR, a nucleic acid or vector encoding said CAR and various uses of said CAR, cell, nucleic acid or vector is disclosed herein. Particularly, a chimeric antigen receptor (CAR) comprising an antigen recognition domain that specifically binds to ENTPD3, is provided.