The presently disclosed subject matter provides for methods and compositions for treating a neoplasia (e.g., multiple myeloma). It relates to chimeric antigen receptors (CARs) that specifically target Fc Receptor-like 5 (FcRL5), e.g., domain 9 of FcRL5, and immunoresponsive cells comprising such CARs. The presently disclosed FcRL5-targeted CARs have enhanced immune-activating properties, including anti-tumor activity.

Compositions and methods are disclosed for targeted treatment of lung cancer-derived metastatic brain tumors. In particular, tumor targeting agents comprising targeting peptides are disclosed that can target a payload, such as a therapeutic or diagnostic agent, to lung cancer-derived metastatic brain tumors. Chimeric antigen receptor (CAR) polypeptides are disclosed that can be used with adoptive cell transfer to target and kill lung cancer-derived metastatic brain tumors.

Provided herein are agents, such as antibodies, antibody-drug conjugates, or chimeric antigen receptors, that target B7-H3. Methods of treating cancer are provided, comprising administering to a patient in need thereof an effective amount of an B7-H3-targeting agent. The patient may be selected for treatment if the cancer expresses an increased level of B7-H3.

Provided herein are immunomodulatory proteins comprising variant PD-L1 and nucleic acids encoding such proteins. The immunomodulatory proteins provide therapeutic utility for a variety of immunological and oncological conditions. Compositions and methods for making and using such proteins are provided.

Genetically engineered T cells expressing a chimeric antigen receptor (CAR) that binds B-cell maturation antigen (BCMA) and uses thereof for treating multiple myeloma, for example, refractory and/or relapsed multiple myeloma. The genetically engineered T cells may comprise a disrupted endogenous TRAC gene and/or a disrupted endogenous β2M gene.

A facilitated method for use in efficient delivery of a pharmaceutical composition over a tissue such as the blood brain barrier and into neurons in the CNS for the treatment of Alzheimer's disease in a mammal, including man is provided. The method is comprising the steps of administrating a therapeutically effective amount of the isolated recombinant Bri2 BRICHOS and lipid microbubbles and enables an increased amount of the isolated recombinant protein to reach the brain to efficiently combat Aβ42 neurotoxicity.

Furthermore, a method for use in enhanced delivery of proteins comprising Bri2 BRICHOS and variants thereof over the blood-brain barrier, facilitating treatment and/or diagnostics of Alzheimer's disease and other neurological diseases is described herein. The method is comprising the steps of administrating a therapeutically effective amount of proteins comprising Bri2 BRICHOS and variants thereof as a first protein moiety coupled to another (non-Bri2) second protein or polypeptide moiety and optionally lipid microbubbles, in the absence of ultrasound treatment.

Compositions, e.g., compositions comprising protein therapeutics, and methods of using such compositions for treating cancer are described.

Chimeric antigen receptors (CARs) with binding domains derived from a novel suite of human 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 are antibodies, fragments thereof, chimeric antigen receptors (CARs) and T cell receptors (TCRs) comprising one or more of the GPC3 binding domains disclosed herein. Provided are compositions, cells and cell therapies comprising the same. Further provided are methods of treatment.

Provided are chimeric antigen receptors (CARs) comprising an NGK2D ecto domain. Provided are compositions, cells and cell therapies comprising the same. Further provided are methods of treatment.