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

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The Eunice Kennedy Shriver National Institute of Child Health and Human Development seeks research co-development partners and/or licensees further to develop and commercialize its novel cells and populations thereof for the treatment of oncological, bacterial, fungal and other conditions.
NIH Reference Number
Product Type
  • Immunotherapy, T Cell Receptor, TCR, CD3, Zeta Chain, Immuno-receptor Tyrosine-based Activation Motif, ITAM, Eunice Kennedy Shriver National Institute of Child Health and Development, NICHD, National Cancer Institute, NCI, Love, Gaud, Hinrichs, Davies
Collaboration Opportunity
This invention is available for licensing and co-development.
Description of Technology

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. 

Potential Commercial Applications
  • Immunotherapy treatment for cancer
  • Immunotherapy treatment for autoimmune diseases
  • Immunotherapy treatment for infectious diseases
  • Autologous cell therapy with pharmaceutical compositions comprising novel cell populations


Competitive Advantages
  • Highly enhanced target antigen reactivity
  • Highly enhanced functional avidity 
  • Cutting-edge therapeutic platform applicable to the treatment of multiple classes of diseases



Paul E Love MD PhD (NICHD/DIR), Guillaume Gaud PhD (NICHD/DIR), Christian Hinrichs MD (NCI), John S Davies Ph.D (NICHD/DIR)

Development Stage
Patent Status
  • Foreign Filed: - Patent Application PCT/US2021/059109, Filed 12 Nov 2021
  • U.S. Provisional: U.S. Provisional Patent Application Number 63/113,428, Filed 13 Nov 2020
Therapeutic Area
Tuesday, February 15, 2022