Photo by Aaron Logan
NEW ORLEANS—Preclinical data suggest IMMU-114, a humanized anti-HLA-DR IgG4 antibody, is active against acute and chronic leukemias.
In a mouse model of chronic lymphocytic leukemia (CLL), IMMU-114 significantly prolonged survival when compared to rituximab.
IMMU-114 also produced a significant survival benefit in a mouse model of acute lymphoblastic leukemia (ALL) that is refractory to doxorubicin.
These results were presented at the 2016 AACR Annual Meeting (abstract 587). The research was carried out by employees of Immunomedics, Inc., the company developing IMMU-114.
The researchers generated a mouse model of human CLL by growing the cell line JVM-3 in SCID mice. The team noted that this model has similar HLA-DR and CD20 expression.
So they compared the efficacy of IMMU-114 and the anti-CD20 antibody rituximab in these mice and found that, at all doses tested, IMMU-114 significantly improved the median survival time (MST).
When both drugs were given at 50 µg, the MST was 42 days with IMMU-114 and 19 days with rituximab (P<0.0001).
When both drugs were given at 100 µg, the MSTs were 54 days and 18 days, respectively (P=0.017). And when both drugs were given at 200 µg, the MSTs were 46 days and 18 days, respectively (P<0.0001).
In control mice that received only saline, the MST was 14 days.
In in vitro experiments with the cell line JVM-3, IMMU-114 and the BTK inhibitor ibrutinib exhibited synergy fighting against the CLL cells. When given with the PI3K inhibitor idelalisib, IMMU-114 produced an additive effect.
In a doxorubicin-refractory mouse model of ALL (MN 60), IMMU-114 provided a significant survival benefit over doxorubicin and saline controls.
The MSTs were 21 days with saline, 23 days with doxorubicin, 39 days with IMMU-114 at 25 µg (P<0.0001), and 42.5 days with IMMU-114 at 50 µg (P<0.0001).
The researchers said IMMU-114 was well tolerated in these experiments, as evidenced by no significant weight loss in the mice.
