Investigation of IL-1RAP in Myeloproliferative Neoplasms: Potential Novel Anti-leukemic Therapy

  • MPNRF | November 29, 2023

    Thrive Award Spotlight :
    Idoroenyi Amanam, MD

    Using our own immune system to treat cancers has become a reality for many solid and blood cancers. “It’s an ideal therapy, as it’s our own specialized system that helps treat abnormal cells,” according to Idoroenyi Amanam, MD, of City of Hope. For MPNs, there is a need to identify new targets for potential immunotherapies.

    Idoroenyi Amanam

    The protein IL-1RAP is selectively overexpressed in MPNs, explains Dr. Amanam, and therefore is an ideal therapeutic target. “Our research is interested in training these cells to target proteins that help stimulate and drive growth of the cancer, with a goal to rid the body of cancer cells.”

    “I believe that MPN is currently one of the most exciting diseases in all of oncology. Traditionally we spent a lot of energy focusing on treating symptoms and watching and waiting for MPNs to progress,” he adds. “We are in an era where we can actually stop these diseases from progressing and even cure some patients. My work hopefully will give patients a chance to live longer.” 

    New immunotherapies, such as bispecific antibodies (BsAb) designed to engage T cells, have shown promising results in treating cancer, including leukemias. BsAbs are artificial (genetically engineered) antibodies that can bridge between target cells and functional molecules to stimulate a directed immune response. 

    Amanam’s group proposes to reduce the toxicity to normal stem cells by using a BsAb to target the stem cells that are expressing IL1RAP and CD3 proteins present on MPN stem cells.  

    IL1RAP expression is involved in the inflammation process and is associated with MPN accelerated and blast phase, and poor overall survival in acute myeloid leukemia (AML). 

    “In myeloid neoplasms (including MPNs), BsAbs that engage CD3 on T cells and a malignant antigen are in clinical trials,” explains Dr. Amanam. “However, these Ags are also frequently expressed on subsets of normal hematopoietic stem cells (HSCs) . . . underscoring the need for more specific and effective targets expressed exclusively on leukemia cells.” 

    Dr. Amanam jokes that as a medical student, he was lured to hematology tumor boards by the free food.” Then he quickly adds: “Dr. Steven Wolff, who was at Meharry at the time, initially peaked my interest, as I was so impressed by the broad use of the biological sciences utilized in diagnosis and therapy of hematology patients.”