Memorial Sloan Kettering Cancer Center

Rutgers, the State University of New Jersey

The Rockefeller University

University of Bonn

Weiyi Wang

Liang Deng

Taha Merghoub

Jedd David Wolchok

Stewart Shuman

Peihong Dai

Ning Yang

Thomas Tuschl

Gunther Hartmann

Roger A Jones

Dinshaw J Patel

Manuel Ascano, Jr

Winfried Barchet

Thomas Zillinger

Pu Gao

Yi Wang

Gregory Mazo

The present disclosure relates to modified vaccinia Ankara (MVA) virus or MVAΔE3L delivered intratumorally or systemically as an anticancer immunotherapeutic agent, alone, or in combination with one or more immune checkpoint blocking agents for the treatment of malignant solid tumors. Particular embodiments relate to mobilizing the host's immune system to mount an immune response against the tumor.

Use of MVA or MVADELTAE3L as immunotherapeutic agents against solid tumors

Disclosed herein are methods and compositions related to the treatment, prevention, and/or amelioration of cancer in a subject in need thereof. In particular aspects, the present technology relates to the use of genetically engineered or recombinant poxviruses, including a modified vaccinia Ankara (MVA) virus comprising a deletion of E3L (MVAΔE3L) engineered to express OX40L (MVAΔE3L-OX40L), an MVA virus comprising a deletion of C7L (MVAΔC7L) engineered to express OX40L (MVAΔC7L-OX40L), a MVAΔC7L engineered to express OX40L and human Fms-like tyrosine kinase 3 ligand (hFlt3L) (MVAΔC7L-hFlt3L-OX40L), an MVA comprising a deletion of E5R (MVAΔE5R), a vaccinia virus comprising a deletion of C7L (VACVΔC7L) engineered to express OX40L (VACVΔC7L-OX40L), a VACVΔC7L engineered to express both OX40L and hFlt3L (VACVΔC7L-hFlt3L-OX40L), a VACV comprising a deletion of E5R (VACVΔE5R), a myxoma virus (MYXV) comprising a deletion of M31R (MYXVΔM31R), or combinations thereof, alone or in combination with other agents, as an oncolytic and immunotherapeutic composition.

Recombinant poxviruses for cancer immunotherapy

The present disclosure relates generally to the fields of oncology, virology and immunotherapy. It concerns poxviruses, specifically the highly attenuated modified vaccinia virus Ankara (MVA), and a recombinant modified vaccinia Ankara virus with deletion of vaccinia virulence factor E3 (MVAΔE3L), each further modified to express human Fms-like tyrosine kinase 3 ligand (Flt3L) or GM-CSF. The disclosure relates to use of the foregoing recombinant viruses as cancer immunotherapeutic agents. The foregoing recombinant poxviruses can also be used in combination with immune checkpoint blockade therapy.

Recombinant MVA or MVADELE3L expressing human FLT3L and use thereof as immuno-therapeutic agents against solid tumors

The present invention relates generally to the fields of oncology, virology and immunotherapy. More particularly, it concerns the use of poxviruses, specifically the replication competent attenuated vaccinia virus with deletion of thymidine kinase (VC-TK) with and without the expression of human Flt3L or GM-CSF as oncolytic and immunotherapy. The foregoing poxviruses can also be used in combination with immune checkpoint blocking agents. The foregoing poxviruses can also be inactivated via Heat or UV-treatment and the inactivated virus can be used as immunotherapy either alone or in combination with immune checkpoint blocking agents.

Replication competent attenuated vaccinia viruses with deletion of thymidine kinase with and without the expression of human Flt3L or GM-CSF for cancer immunotherapy

The present disclosure relates to infection-competent, but nonreplicative inactivated modified vaccinia Ankara (MVA) and its use as immunotherapy, alone, or in combination with immune checkpoint blocking agents for the treatment of malignant solid tumors. Particular embodiments relate to inducing an immune response in a subject diagnosed with a solid malignant tumor.

Use of inactivated nonreplicating modified vaccinia virus Ankara (MVA) as monoimmunotherapy or in combination with immune checkpoint blocking agents for solid tumors

The present invention relates generally to the fields of oncology, virology and immunotherapy. More particularly, it concerns the use of a recombinant modified vaccinia Ankara (MVA) virus comprising an MVA harboring a human Fms-like tyrosine kinase 3 ligand (hFlt3L) (MVA-hFtl3L). The foregoing vaccinia Ankara (MVA) virus can be delivered to tumor cells of a subject afflicted with a malignant solid tumor, to treat the tumor. In a related aspect, the present disclosure concerns a recombinant modified vaccinia Ankara virus with deletion of vaccinia virulence factor E3 (MV At.E3L) modified to express human Fms-like 5 tyrosine kinase 3 ligand (hFlt3L) isolated, suitable for use as an immunotherapeutic agent against a malignant solid tumor.

Recombinant MVA or MVA&#x394;E3L expressing human FLT3L and use thereof as immuno-therapeutic agents against solid tumors

The present disclosure relates to modified vaccinia Ankara (MVA) virus or MVA&#x394;E3L delivered intratumorally or systemically as an anticancer immunotherapeutic agent, alone, or in combination with one or more immune checkpoint blocking agents for the treatment of malignant solid tumors. Particular embodiments relate to mobilizing the host's immune system to mount an immune response against the tumor.

Use of MVA or MVA&#x394;E3L as immunotherapeutic agents against solid tumors

Replication competent attenuated vaccinia viruses with deletion of thymidine kinase with and without the expression of human FLT3L or GM-CSF for cancer immunotherapy

The present disclosure relates generally to the fields of oncology, virology and immunotherapy. It concerns poxviruses, specifically the highly attenuated modified vaccinia virus Ankara (MVA), and a recombinant modified vaccinia Ankara virus with deletion of vaccinia virulence factor E3 (MVA&#x394;E3L), each further modified to express human Fms-like tyrosine kinase 3 ligand (Flt3L) or GM-CSF. The disclosure relates to use of the foregoing recombinant viruses as cancer immunotherapeutic agents. The foregoing recombinant poxviruses can also be used in combination with immune checkpoint blockade therapy.

The present disclosure relates to modified vaccinia Ankara (MVA) virus or MVAAE3L delivered intratumorally or systemically as an anticancer immunotherapeutic agent, alone, or in combination with one or more immune checkpoint blocking agents for the treatment of malignant solid tumors. Particular embodiments relate to mobilizing the host's immune system to mount an immune response against the tumor.

The present invention provides STING crystals. The present invention also provides STING modulators that interact with sites present in and/or defined by such crystals. The present invention also provides methods of making and using such crystals and modulators. Other aspects and/or features of the present invention will be apparent to those skilled in the art, reading the present specification.

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New York, NY, United States of America

Weiyi Wang