Enhanced Antigen Reactivity of Immune Cells Expressing a Mutant Non-Signaling CD3 Zeta Chain

Immunotherapy is a cutting-edge new category of treatment that aims to harness and, in some cases, modify the patient’s own immune cells to improve their ability to cure diseases. It can be an effective approach for a variety of conditions, ranging from cancer to inflammatory diseases.  However, a number of obstacles to the overall success of immunotherapy still exist.  For example, reactivity against a target antigen can be attenuated or the lifespan of the “modified” immune cells can be too short. In cancer, some tumor cells could express antigen with very low reactivity, thus remaining undetected by “classical” immune cells.   Despite considerable research in the field of immunotherapy, there still exists a need for improved methods and products.

This technology describes the method of enhancing an antigen-specific immune response in a subject. This is accomplished through the modification of a CD3 subunit chain or related non-CD3 subunit chain which functions to transduce signals through immune receptors – such as the T cell antigen receptor. The specific subunit chain modifications are comprised of one or more of: (a) at least one Immuno-receptor Tyrosine-based Activation Motif (ITAM) deletion; or (b) at least one exogenous intracellular hematopoietic cell signaling domain; and (c) at least one modified ITAM comprising an amino acid sequence of Formula I. 

Researchers at the Eunice Kennedy Shriver National Institute of Child Health and Human Development are highly motivated in seeking licensing and/or collaboration partners to develop therapeutic cell populations arising out of these technologies.  An ideal partner would enter into both a Cooperative Research and Development Agreement (CRADA) and an exclusive license agreement towards commercialization of one or more therapies to treat various oncologies.