Other

Geneius Biotechnology, Inc.

Alfred E Slanetz

Alfred L Bothwell

The invention involves generating a T cell response to subdominant antigens and using the cells to therapeutically change the cellular homeostasis and nature of the immune response. In a preferred embodiment, the cells are generated outside of the patient avoiding the influence of the patient's immunologic milieu. By stimulating and growing the T cells from a patient in a tissue culture to one or more subdominant antigens and the transplanting them into the patient, if enough cells are expanded and transplanted, the transplanted cells overwhelm the endogenous dominant T cells in the response to either break or induce immune tolerance or otherwise modify the immune response to the cells or organism expressing that antigen. When the memory cells are established they are then reflective of this new immunodominance hierarchy so that the desired therapeutic effect is long lasting. In effect, the transplantation exogenously generated T cells reactive to the subdominant antigens is recapitulating priming and rebalancing the patient's immune response to target previously subdominant antigens in the cells or organism to produce a therapeutic benefit.

Modulated immunodominance therapy

An intact, assembled T cell receptor (TcR) in soluble form is provided. The soluble TcR is prepared by splicing the extracellular domains of a T cell receptor to the glycosyl phosphatidylinositol (GPI) membrane anchor sequences of Thy-1. The molecule is expressed in the absence of CD3 on the cell surface, and can be cleaved from the membrane by treatment with phosphatidylinositol specific phospholipase C (PI-PLC). The .alpha. and .beta. chains of the soluble molecule are paired in the native conformation as judged by reactivity with the anti-V.sub..beta. 8 monoclonal antibody F23.1, and with the anti-clonotypic monoclonal antibody 1B2. The soluble TcR is a disulfide linked dimer with a molecular mass of 95 kDa on SDS-PAGE under nonreducing conditions, and 47 kDa after reduction.

Growing community of inventors

Cohasset, MA, United States of America

Alfred E Slanetz