University of California

The United States Government As Represented by the Department of Veterans Affairs

Sherven Sharma

Steven M Dubinett

Leonard H Rome

Valerie A Kickhoefer

Upendra K Kar

Jian Yang

Cheryl I Champion

Kathleen A Kelly

Linda M Liau

Jay M Lee

Isaac Yang

Janina Jiang

Cheryl Champion

The invention relates to compositions of vault complexes containing recombinant cytokine fusion proteins that include a cytokine and a vault targeting domain, and methods of using the vault complexes to deliver the cytokines to a cell or subject, and methods for using the compositions to treat cancer, such as lung cancer.

Vault complexes for cytokine delivery

The invention is based on the disclosure provided herein that secondary lymphoid organ chemokine (SLC) inhibits the growth of syngeneic tumors in vivo. Thus, the invention provides a method of treating cancer in a mammal subject by administering a therapeutically effective amount of an SLC to the mammal in combination with a checkpoint inhibitor, including monoclonal antibodies and small molecule inhibitors. Exemplary checkpoint molecules include CTLA-4, a CTLA-4 receptor, PD-1, PD1-L1, PD1-L2, 4-1BB, OX40, LAG-3, TIM-3 or a combination thereof. SLCs useful in the methods of the invention include SLC polypeptides, variants and fragments and related nucleic acids.

Combination immunotherapy

The invention relates to compositions of vault complexes for use as adjuvants for stimulating a cellular immune response to an antigen, for example a tumor antigen, and methods of using the vault complexes in the treatment of diseases, such as cancer.

Vault immunotherapy

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Culver City, CA, United States of America

Sherven Sharma