University of Notre Dame Du Lac

University of Massachusetts

University of Connecticut

Brian M Baker

Pramod K Srivastava

Brian Gregory Pierce

Zhiping Weng

Lance Hellman

Described herein are methods of identifying immunologically protective neo-epitopes from the cancer tissue DNA of cancer patients using biophysical principles as well as bioinformatics techniques. The identification of immunologically protective neo-epitopes provides pharmaceutical compositions with a limited number of tumor-specific peptides suitable for personalized genomics-driven immunotherapy of human cancer. Specifically disclosed herein is a method of using the conformational stability of an epitope in an MHC protein-binding groove to predict immunogenicity of peptides in a putative neo-peptide set from a tumor from a cancer patient. Pharmaceutical compositions and methods of administration are also included.

Identification of immunologically protective neo-epitopes for the treatment of cancers

Molecular constructs and dual recognition constructs having a sequence encoding a TCR affinity weakening motif, and DNA and RNA sequences corresponding thereto, are presented. Modified T-cells and other cells transformed with the molecular contracts express a modified TCR that imparts a reduction, in non-specific binding, -an enhancement of binding specificity and an enhancement of binding affinity for a target antigen, compared to non-transformed (wild-type, native) T-cells, are described. The modified TCRs possess an affinity enhancing motif and an affinity weakening motif. Methods of transforming cells and methods of using enriched populations of transformed cells, in the treatment of cancer and infections arid T-cell mediated pathologies are provided. The affinity weakening motif imparts a weakened interaction, of a TCR with major histocompatibility complex proteins, such as HLA proteins in humans. Soluble modified TCRs are also provided, Therapeutic preparations comprising modified T-cells, modified TCRs, and modified TCR-therapeutic agent-conjugates, are also provided.

Molecular constructs and uses thereof

The instant disclosure provides a microscale method for providing correctly folded, and assembled biologically active proteins in an efficient and shorted time frame, compared to conventional protein production techniques. Proteins produced from inclusion bodies and other aggregated protein sources are provided. Microscale production of correctly folded and assembled class I MHC protein and complexes thereof are also provided for, as well as for high throughput production for use in epitope discovery protocols. Microscale production of complex proteins from protein aggregates and preparations containing protein aggregates is provided that requires less than 24 hours of processing time.

Protein folding and methods of using same

High-affinity variants of the DMF5 TCR, and methods of use thereof for the treatment and imaging of cancer in a patient.

Growing community of inventors

Granger, IN, United States of America

Brian M Baker