Combination immunotherapy
AssigneesThe Regents of the University of California, The United States Government as represented by the Department of Veterans Affairs
InventorsSteven M. Dubinett, Sherven Sharma, Jay M. Lee
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Abstract
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.
Claims9
A method for inhibiting the growth of a non-small cell lung carcinoma (NSCLC) solid tumor in a human subject comprising
- a. administering to the subject intratumorally, at the tumor site or to a lymph node proximal to the tumor, an autologous antigen presenting cell comprising an expression vector comprising a polynucleotide encoding a CCL21 polypeptide comprising the amino acid sequence SEQ ID NO:1, wherein the cell expresses and secretes the CCL21 polypeptide, and
- b. administering to the subject a human PD-L1 inhibitor selected from BMS-936559 (BMS/Ono), MPDL3280A (Roche/Genentech), MEDI-4736 (Medimmune), and MSB0010718C (Merck/Serono), wherein the cell is administered to the subject prior to, about 2 weeks prior to, about 3 weeks prior to, or at the same time as, the human PD-L1 inhibitor;
- and wherein the combination of said administrations exhibits synergistic anti-tumor effects.
Dependencies are inferred from the claim text.