Wisconsin Alumni Research Foundation

Leland Stanford Junior University

Debra Bloom

C Garrison Fathman

Peiman Hematti

Hans W Sollinger

Gregory Ford

Arjang Djamali

Sarah Slaymaker

The present disclosure relates to methods, cells, and compositions for preparing T cell populations and compositions for adoptive cell therapy. In particular, provided herein are methods for efficiently expanding and activating T cell populations for genetic engineering and adoptive T cell immunotherapies. Also provided are cells and compositions produced by the methods and methods of their use.

Methods of T cell expansion and activation

The invention relates to methods, compositions, and kits for detection of biomarkers. In one embodiment, the invention relates to a method for detecting AMR biomarkers in a biological sample. In another embodiment, the invention relates to a method for detecting, monitoring, diagnosing and predicting antibody mediated rejection. In yet another embodiment, the invention relates to a method for monitoring a subject for antibody mediated rejection comprising detecting BAFF or a BAFF variant in a biological sample. In still another embodiment, the invention relates to a kit for detecting BAFF in a urine sample.

Detection of B-cell activating factor as a biomarker for antibody mediated rejection in transplant recipients

Isolated nucleic acid compositions and sequences of anergy associated genes are provided, including the novel GRAIL gene. Expression of these genes is upregulated during the early stages of induction of anergy. The murine GRAIL sequence is shown to attenuate IL-2 transcription in T cells during response to antigenic stimulation. The identification of genes involved in the induction of anergy is useful in the evaluation of the pathophysiology or immunotherapy of cancer, autoimmune disease, and transplant rejection. Genetic sequences involved in anergy induction are useful markers in the evaluation of specific immunotherapies. Functional characterization of genes involved in anergy induction allows the elucidation of the mechanism(s) of T cell anergy, including the transcriptional blockade of IL-2, which may be manipulated to regulate T cell responses in human disease. The signaling pathways involving GRAIL are of significant interest in the identification of drugs that either block or upregulate the function(s) of GRAIL.

Anergy associated genes

Methods and compositions are provided for identifying genes associated with induction of anergy in T-cells and the use of the nucleic acids or proteins as diagnostics for monitoring induction of tolerance for the presence of tolerized T-cells in a physiological sample, or elucidating the pathway to anergy or activation in T-cells. A cysteine string protein is found to indicate quiescent T-cells and is lost with anergic T-cells.

Growing community of inventors

Sun Prairie, WI, United States of America

Debra Bloom