Johns Hopkins University

Juan Fu

Drew M Pardoll

Young Jun Kim

Duojia Pan

Fan Pan

Joseph Barbi

William R Bishai

Charles George Drake

John R Murphy

Laurene Cheung

Cynthia K Bullen

Pankaj Kumar

Meghan Davis

Amit Kumar

Sadiya Parveen

Vijayan Sambasivam

Sumit Siddharth

Dipali Sharma

Ying Zheng

Andriana Lebid

The present invention relates to compositions and methods for treating cancer by targeting the Activin signaling pathway. In certain embodiments, combining Activin blockade with immunomodulation alters regulatory T (Treg) cell-mediated immune regulation and treats cancer.

Compositions and methods for targeting activin signaling to treat cancer

The present invention is related to a method of treating or preventing cancer in a subject comprising administering to a subject having cancer or prone of getting cancer a first agent that depletes the subject's regulatory T cells (Tregs); followed by administering to the subject a second agent comprising a checkpoint inhibitor.

Methods of treating or preventing cancer with an agent that depletes tregs and a checkpoint inhibitor

We formulated multiple TLR agonists into GVAX (lethally irradiated tumor cell vaccines engineered to secrete GM-CSF). Specifically, GLA and R848, TLR4 and TLR7/8 agonists found to be safe in patients, were formulated with GVAX (TEGVAX&#x2014;for TLR agonists enhanced GVAX), and this formulation was effective in producing anti-tumor responses in 3 different preclinical models, including palpable B16. These anti-tumor responses were correlated with increased CD4 and CD8 T-cells that can secrete IFN&#x3b3; circulating in the tumor microenvironment as well as significantly higher level of p15E specific CTL mediated cell killing in mice treated with TEGVAX in comparison to controls. When combined with anti-PD-1 antibody, TEGVAX was able to induce regression of established B16 tumors.

Cancer immunotherapy

The invention provides provides immunogenic compositions comprising neoplastic cells expressing a cytokine (GM-CSF) formulated with at least one TLR agonist and methods of using the composition to induce or enhance an immune response.

Immunogenic compositions and methods for treating neoplasia

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Baltimore, MD, United States of America

Juan Fu