H. Lee Moffitt Cancer Center and Research Institute, Inc.

The Wistar Institute

University of South Florida

Memgen, Inc.

Scott Antonia

Dmitry Gabrilovich

Claudio Anasetti

Frederick L Locke

Dario C Altieri

Mark L McLaughlin

David L Morse

Mark J Cantwell

Sunil D Chada

Shari Pilon-Thomas

Kerstin Menander

Amer A Beg

Dmitry I Gabrilovich

Dario Altieri

The invention concerns a variant (double mutant form) of the survivin polypeptide; nucleic acid molecules encoding the survivin variant; antigen presenting cells (APCs) such as dendritic cells, or APC precursors, comprising the variant survivin polypeptide or encoding nucleic acid sequence; and methods for treating a malignancy, such as myeloma, or for inducing an immune response, utilizing a variant survivin polypeptide, nucleic acid molecule, or APC.

Variant survivin vaccine for treatment of myeloma

The invention concerns APCs, such as DCs, comprising a combination of an exogenous type I interferon and an exogenous CD40-L or one or more heterologous nucleic acid sequences encoding a combination of an exogenous type I IFN and an exogenous CD40-L, such as a combination of IFNβ and CD40-L; and methods for treating a malignancy by administering such APCs to a subject in need thereof. In certain embodiments, a subject is treated with an irradiation therapy before administering the APCs, such as DCs, of the invention. The invention also concerns an oncolytic virus comprising a combination of a type I IFN and CD40-L or one or more nucleic acid sequences encoding a combination of a type I IFN and CD40-L, such as a combination of IFNβ and CD40-L; and methods for treating a malignancy by administering such oncolytic virus to a subject in need thereof.

Oncolytic virus or antigen presenting cell mediated cancer therapy using type I interferon and CD40-ligand

A method is disclosed for treating small cell lung cancer (SCLC) in a subject that involves administering to the subject a therapeutically effective amount of dendritic cells engineered to overexpress p53. In some embodiments, the method further involves administering to the subject a therapeutically effective amount of all-trans-retinoic acid (ATRA). The method can also involve administering to the subject a therapeutically effective amount of an immune checkpoint inhibitor.

Combination immunotherapy for treating cancer

A method is disclosed for treating a cancer in a subject. The method comprises administering to the subject a composition comprising a therapeutically effective amount of a checkpoint inhibitor and a therapeutically effective amount of a tumor vaccine. In some embodiments, the tumor vaccine comprises radiated autologous tumor cells and a cell line engineered to express GM-CSF and CD40 ligand. In some embodiments, the checkpoint inhibitor comprises an anti-PD-1 antibody (e.g., BMS 936558), anti-PD-L1 antibody (e.g., cloneM1H1), anti-CTLA-4 antibody (e.g., Ipilimumab, BMS), or any combination thereof.

GM-CSF/CD40L vaccine and checkpoint inhibitor combination therapy

The current invention pertains to a molecular conjugate comprising an antagonist of a cell surface receptor specific to a target cell and an immune effector, such as a T cell modulator, conjugated to the antagonist. The target cell can be a cell responsible for development of a disease in a subject, for example, a cancer cell. In certain embodiments, the immune effector is an immune effector protein or an immune effector fragment thereof. The current invention also pertains to a method of treating a disease in a subject, the method comprising administering to the subject a pharmaceutically effective amount of the molecular conjugates of the current invention to the subject. The methods of the current invention can be used to treat cancer, such as breast cancer, ovarian cancer, prostate cancer, lung cancer, pancreatic cancer, or melanoma.

Conjugates for immunotherapy

Double mutant survivin vaccine

The present invention relates to immunotherapy methods for treating hyperproliferative disease in humans, particularly to hyperproliferative disease that is refractory to therapy. More specifically, the invention is directed, in one embodiment, to methods for treating a subject with a hyperproliferative disease in which the expression of a self gene is upregulated in therapy-resistant hyperproliferative cells. In another embodiment, an adenoviral expression construct comprising a self gene under the control of a promoter operable in eukaryotic cells is administered to the therapy-resistant hyperproliferative cells. The present invention thus provides immunotherapies for treating therapy-resistant hyperproliferative disease by attenuating the natural immune system's CTL response against hyperproliferative cells or overexpressing mutant p53 antigens, for example.

P53 vaccines for the treatment of cancers

Growing community of inventors

Land O Lakes, FL, United States of America

Scott Antonia