Duke University

The United States of America, As Represented by the Secretary, Department of Health and Human Services

Argos Therapeutics, Inc.

Smita K Nair

Eli Gilboa

David J Boczkowski

Darell D Bigner

Matthias Gromeier

Vidyalakshmi Chandramohan

Ira H Pastan

David H Ashley

Michael Brown

Xuhui Bao

Methods of testing tumor samples for mutational burden and/or for expression profiles permit the prediction of responsiveness of an individual to immunotherapy comprising PVSRIPO. Those predicted to respond are treated with PVSRIPO and those predicted not to respond are treated with other agents.

Methods for predicting tumor response to immunotherapy

Chimeric poliovirus is capable of activating antigen presenting cells. The activation of the antigen presenting cells may be in vitro, ex vivo, or in vivo. The activated antigen presenting cells may be administered alone or with an antigen or vaccine. The activated antigen may be loaded in vitro or ex vivo with antigen to form antigen-loaded, activated, antigen presenting cells. These may be administered therapeutically. Therapeutic administration of antigen presenting cells may be used as an adjuvant to other therapies.

Compositions and methods for activating antigen presenting cells with chimeric poliovirus

Regional, tumor-targeted, cytotoxic therapy, such as D2C7-immunotoxin (D2C7-IT), not only specifically target and destroy tumor cells, but in the process initiate immune events that promote an in situ vaccine effect. The antitumor effects are amplified by immune checkpoint blockade which engenders a long-term systemic immune response that effectively eliminates all tumor cells.

Combination therapy of immunotoxin and checkpoint inhibitor

Human clinical use of a chimeric poliovirus construct has demonstrated excellent anti-tumor effect. Combination with immune checkpoint inhibitors increases the anti-tumor effect. Tumors of different types are susceptible to the combination treatment, including but not limited to melanoma, glioglastoma, renal cell carcinoma, prostate cancer, breast cancer, lung cancer, medulloblastoma, and colorectal cancer.

Combination treatment

Disclosed are cells and methods for treating or preventing tumor formation or infections with pathogens in a patient. The cells of the invention are antigen-presenting cells (e.g., dendritic cells or macrophage) that have been loaded with RNA derived from tumors or pathogens. By administering the RNA-loaded antigen-presenting cells to a patient, tumor formation or pathogen infections can be treated or prevented. Alternatively, the RNA-loaded cells can be used as stimulator cells in the ex vivo expansion of CTL. Such CTL can then be used in a variation of conventional adoptive immunotherapy techniques.

Methods for treating cancers and pathogen infections using antigen-presenting cells loaded with RNA

A method for eliciting an immune response to an antigen in a subject via (a) loading isolated antigen presenting cells with an antigen ex vivo; and (b) administering the antigen presenting cells to a subject at a pre-treated site.

In situ maturation of dendritic cells

The present invention relates to cells and methods for treating or preventing tumor formation or infections with pathogens in a patient. The cells of the invention are antigen-presenting cells (e.g., dendritic cells or macrophage) that have been loaded with RNA derived from tumors or pathogens. By administering the RNA-loaded antigen-presenting cells to a patient, tumor formation or pathogen infections can be treated or prevented. Alternatively, the RNA-loaded cells can be used as stimulator cells in the ex vivo expansion of CTL. Such CTL can then be used in a variation of conventional adoptive immunotherapy techniques.

The present invention relates, in general, to RNA-loaded antigen presenting cells and, in particular, to methods for treating or preventing tumor formation or pathogen infection in a patient. The invention further relates to methods of monitoring T-cell stimulation and to methods of antigen discovery.

RNA-loaded antigen presenting cells

Method of identifying tumor antigens that elicit a T-cell response

Methods for treating cancers and pathogen infections using

Disclosed is a method for presenting an antigen in the form of a peptide on the surface of a cell. The method involves inhibiting the activity of an MHC class I pathway-associated component (e.g., a TAP protein or a proteasome or its components) in a cell and contacting the cell with an antigenic peptide to produce a potent antigen presenting cell. The antigen presenting cells of the invention can be administered to a mammal in a method of treating or preventing cancer or infection with a pathogen (e.g., a bacterium or virus). If desired, the antigen presenting cells can be used to stimulate CTL proliferation in vitro, and the resulting effector cells can subsequently be administered to a mammal in a method of therapy.

Growing community of inventors

Durham, NC, United States of America

Smita K Nair