Anti-LILRB4 CAR-T cells for the treatment of relapsed or refractory pediatric acute myeloid leukemia

Acute myeloid leukemia is a type of blood cancer that occurs in children and adults, requiring intensive treatment with chemotherapy and many times stem cell transplant. Despite aggressive therapy, nearly half of children with AML will relapse and a majority will die from this disease. In addition, in some patients with another form of leukemia called B-ALL, their leukemia can change to AML after using immunotherapy based treatments. This is called lineage switch (LS) AML, and while rare, is almost universally fatal with reported survival of ~10%. Novel treatments are desperately needed to improve outcomes for this group of patients.
Our research team has developed and validated a CAR-T cell directed against a novel target on AML called leukocyte immunoglobulin like receptor B4 (LILRB4). In normal cells, this target displays a restricted pattern of expression only to cells of the monocytic lineage, but importantly, is not expressed on normal stem or progenitor cells of the bone marrow. We have demonstrated LILRB4 is highly expressed on the complete population of monocytic AML cells and importantly continues to be expressed in cases of LS AML following immunotherapy. This makes LILRB4 an attractive target for cell-based immunotherapy for patients with R/R acute leukemia with limited effective treatment options. Indeed, in several preclinical models, we have demonstrated LILRB4 targeting CAR-T cells eliminate AML cells, while sparing normal stem and precursor cells of the bone marrow.
In this project we will test anti-LILRB4 CAR-T cells in pediatric patients with relapsed, refractory or LS AML in a "first in human" Phase 1 clinical trial. The goal of this trial is to determine safety of this novel cell therapy by evaluating for potential serious side effects and toxicities. We will increase the dose of cells given following establishing safety rules to determine a dose that is well tolerated, so we can test if this treatment is effective. We will also determine if patients are able to go into remission, and how long this lasts for. We will also be gathering important information to learn if these CAR-T cells effect surrounding normal cells in the bone marrow or body. Other data we obtain from this trial will help us potentially uncover ways to overcome leukemia cell resistance to immunotherapy or other treatments.
Importantly, this trial will include pediatric patients aged 1 year and older. We believe this is important as young pediatric patients comprise a large portion of patients with the specific type of AML being targeted on this study called "monocytic AML". Patients whose disease has not responded to or relapsed after chemotherapy, immunotherapy and/or stem cell transplant may be able to participate in this study if no other treatment options are available.
Through support of this work, we believe this novel CAR-T cell has the potential to offer a curative treatment option for patients with LILRB4+ relapsed or refractory acute myeloid leukemia.