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NEO-212 Shows Promise In Treating Acute Myeloid Leukemia

July 6, 2021

Potentially Curative Therapeutic Activity of NEO212, a Perillyl Alcohol-Temozolomide Conjugate, in Preclinical Cytarabine-Resistant Models of Acute Myeloid Leukemia.

Authors: Axel H. Schönthal 1, Steve Swenson2, Radu O. Minea2, Hye Na Kim3, Heeyeon Cho2, Nazleen Mohseni1, Yong-Mi Kim3, Thomas C. Chen2

Acute Myeloid Leukemia (AML) is difficult to treat cancer that starts in the bone marrow and then moves quickly into the blood allowing it to spread to other parts of the body including the lymph nodes, liver, spleen, and central nervous system. Despite progress in the treatment of AML, the clinical outcome remains low and many patients are still dying from this disease. First-line treatment consists of chemotherapy, which typically includes cytarabine (AraC), either alone or in combination with anthracyclines, but drug resistance can develop and significantly worsen prognosis.

In a recent trial, NeOnc Technologies studied its NEO-212 conjugate to see if it might have an impact in treating this persistent form of cancer. In several in vitro and in vivo trials, human HL60 and U937 AML cell lines, as well as different AraC-resistant AML cell lines, were treated with NEO212 to study the effect of the and effects on cell proliferation, cell cycle, and cell death. The results of the in vitro experiments showed that treatment of cells with NEO212 results in growth inhibition via potent G2 arrest, which is followed by apoptotic cell death. Additionally, NEO212 was equally potent in highly AraC-resistant cells. The in vivo studies showed that NEO212 treatment strikingly extended survival of the test animals and the majority of those treated with NEO-212 continued to thrive and survive without any signs of illness. These results, along with the absence of side effects, suggest that NEO212 should be developed further toward clinical testing in treating AML.

1Department of Molecular Microbiology & Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA; nmohseni@usc.edu, 2Department of Neurosurgery, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA; sswenson@usc.edu (S.S.); minea@usc.edu (R.O.M.); heeyeonc@usc.edu (H.C.), 3Department Pediatrics, Division of Hematology, Oncology, Blood and Bone Marrow Transplantation, Children’s Hospital of Los Angeles, Los Angeles, CA 90027, USA; hyekim@chla.usc.edu (H.N.K.); ymkim@chla.usc.edu (Y.-M.K.),