Cimeio Therapeutics Announces Publication of Seminal Epitope Editing Work in the Journal of Experimental Medicine
— Research demonstrates that engineering the epitope of the cell surface protein CD123 in hematopoietic stem cells protects them from targeted therapies —
— Epitope edited hematopoietic stem cells could reduce heme toxicity of targeted therapies —
Basel, Switzerland, September 29, 2023
Cimeio Therapeutics, a biotechnology company that is reimagining immunotherapy with its Shielded Cell and Immunotherapy (SCIP®) platform, along with Prof. Lukas Jeker’s team at the Department of Biomedicine (DBM) at the University of Basel, today announced the publication of research in the Journal of Experimental Medicine showing that epitope edited human hematopoietic stem cells (HSCs) can be protected from targeted immunotherapies. The findings have broad implications for the development of novel therapies for hematologic conditions and the emerging field of epitope editing.
The paper, led by DBM scientists Romina Marone, Emmanuelle Landmann, Anna Devaux and Rosalba Lepore, demonstrated that using epitope-engineering, a novel approach the researchers first pioneered in their laboratory, human HSCs could be protected from a CD123-targeted immunotherapy. This is important because the CD123 receptor is present on both healthy blood cells and an aggressive form of blood cancer called Acute Myeloid Leukemia (AML). By ‘shielding’ the healthy HSCs, a CD123-directed therapy would only kill the cancer cells, sparing the patient the toxicity associated with depleting healthy blood cells that often greatly limits the utility of these targeted immunotherapies.
“By exchanging a single amino acid, we could prevent potent immunotherapies from depleting cells, while the edited cells remained healthy and functional.,” said Lukas T. Jeker, M.D., Ph.D., co-founder of Cimeio and Professor of Experimental Transplantation Immunology & Nephrology at the Department of Biomedicine, University of Basel and at the Basel University Hospital, Switzerland.
This seminal work is the basis of a new field of research called epitope editing, which has the potential to enable the development of therapies for patients with numerous hematologic diseases not previously possible. The foundational patent for epitope editing is exclusively licensed to Cimeio.
The problem of potentially useful targets also being present on healthy tissue is not an issue unique to CD123. There have been many targeted therapies developed for hematologic conditions that ultimately failed because the toxicity that resulted from depleting healthy cells was too great.
“Given the advent of epitope shielding, we are now able to develop very powerful therapies against targets that we previously could not safely drug. Potent targeted therapies include antibodies, antibody-drug conjugates, T cell engagers, and even CAR T cells,” said Stefanie Urlinger, Ph.D., Chief Scientific Officer at Cimeio Therapeutics. “This novel approach to drug development is changing the landscape for blood and bone marrow cancers, autoimmune, and genetic diseases.”
Along with CD123, Cimeio is developing epitope engineered cells and targeted therapies for CD45, CD117, and several other targets.
Cimeio is a biotechnology company developing Shielded-Cell & Immunotherapy Pairs™ (SCIP), novel immunotherapies which have the potential to transform treatment of hematologic diseases. Cimeio develops immunotherapies, along with paired, modified variants of naturally occurring cell surface proteins in HSCs. These novel epitope edited variants maintain their function but are resistant to depletion when targeted by a paired immunotherapy which has high affinity for the wild-type version of these proteins. These immunotherapies have significant therapeutic potential, which Cimeio is using to develop curative treatments for patients with hematologic malignancies, autoimmune disorders, and genetic diseases. Shielded Cell and Immunotherapy Pairs and SCIP are trademarks of Cimeio Therapeutics, Inc. For more information, please visit www.cimeio.com.
Targeted eradication of transformed or otherwise dysregulated cells using monoclonal antibodies (mAb), antibody–drug conjugates (ADC), T cell engagers (TCE), or chimeric antigen receptor (CAR) cells is very effective for hematologic diseases. Unlike the breakthrough progress achieved for B cell malignancies, there is a pressing need to find suitable antigens for myeloid malignancies. CD123, the interleukin-3 (IL-3) receptor alpha-chain, is highly expressed in various hematological malignancies, including acute myeloid leukemia (AML). However, shared CD123 expression on healthy hematopoietic stem and progenitor cells (HSPCs) bears the risk for myelotoxicity. We demonstrate that epitope-engineered HSPCs were shielded from CD123-targeted immunotherapy but remained functional, while CD123-deficient HSPCs displayed a competitive disadvantage. Transplantation of genome-edited HSPCs could enable tumor-selective targeted immunotherapy while rebuilding a fully functional hematopoietic system. We envision that this approach is broadly applicable to other targets and cells, could render hitherto undruggable targets accessible to immunotherapy, and will allow continued posttransplant therapy, for instance, to treat minimal residual disease (MRD).