Date: 2016-04-18
Type of information: Presentation of results at a congress
phase: preclinical
Announcement: presentation of results at the American Association for Cancer Research (AACR) Annual Meeting
Company: Immunomedics (USA - NJ)
Product: IMMU-114
Action
mechanism: monoclonal antibody. IMMU-114 is a novel humanized antibody directed against an immune response target, HLA-DR, for the treatment of patients with B-cell cancers. HLA-DR is a receptor located on the cell surface whose role is to present foreign objects to the immune system for the purpose of eliciting an immune response. Increased presence of HLA-DR in hematologic cancers has made it a prime target for antibody therapy. Although other anti-HLA-DR antibodies have been developed, IMMU-114 is distinguished by having a different immunoglobulin class, IgG4, which does not function by the usual effector-cell activities of antibodies, such as complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC). As a result, IMMU-114 does not rely on an intact immune system in the patient to kill tumor cells. Furthermore, because ADCC and CDC are believed to play a major role in causing the side effects of antibody therapy, we expect IMMU-114 to be less toxic to patients. By targeting HLA-DR, a receptor that is different from the antigen targeted by rituximab or other antibodies in development for NHL and other B-cell malignancies, IMMU-114 may represent a new tool in the arsenal to combat these cancers.
Disease: chronic lymphocytic leukemia, acute lymphoblastic leukemia
Therapeutic area: Cancer - Oncology
Country:
Trial details:
Latest
news: * On April 18, 2016, Immunomedics reported that, in a preclinical model of human chronic lymphocytic leukemia (CLL), IMMU-114, was superior to anti-CD20 therapy using rituximab, and had an additive effect when combined with kinase inhibitors. Furthermore, IMMU-114 also achieved a significant survival benefit in an animal model of human acute lymphoblastic leukemia (ALL) that is refractory to doxorubicin.
In a Phase 1, first-in-man dose-escalation study, the anti-HLA-DR antibody, as a subcutaneous monotherapy, has produced encouraging clinical responses in patients with relapsed/refractory non-Hodgkin lymphoma (NHL) and CLL, including one NHL patient with a complete response. The current preclinical study was undertaken to further evaluate the activity of IMMU-114 in CLL and ALL, as compared to anti-CD20 or doxorubicin therapy, respectively, as well as in combination with kinase inhibitors in CLL.
In a mouse model of human CLL that has similar HLA-DR and CD20 expression, IMMU-114 significantly improved median survival time (MST) of 19 days for the rituximab group to more than 42 days, even at doses as low as 50 µg (P<0.0001) (Table 1).
In cell culture experiments with a CLL line, IMMU-114 and ibrutinib, the Bruton’s kinaseinhibitor, were found to provide a synergistic growth inhibitory interaction, whereas the combination with idelalisib, a PI3K-inhibitor, produced an additive effect. These results suggest that IMMU-114 could potentially improve the results of other agents used in the therapy of patients with CLL.
For ALL, in a doxorubicin-refractory animal model, IMMU-114 therapy provided a significant survival benefit (MST>39 days) at doses as low as 25 µg, compared to both doxorubicin-treated and saline control animals (MST=23 and 21 days, respectively, P<0.0001) (Table 2).
