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: Innate Pharma (France)
Product: monalizumab (IPH2201) and durvalumab
Action
mechanism:
- monoclonal antibody/immune checkpoint inhibitor. Monalizumab (IPH2201/anti-NKG2A) is a first-in-class humanized IgG4 antibody. NKG2A is a checkpoint receptor that inhibits anti-cancer functions of cytotoxic NK and T lymphocytes. NKG2A recognises HLA-E ligands, and by expressing HLA-E cancer cells can protect themselves from killing by CD94/NKG2A-positive NK-, NKT-, and T-cells (a/b and g/d). HLA-E is frequently up-regulated on cancer cells and this occurs in patients with different types of solid tumours or haematological malignancies. In some types of cancers, high-levels of HLA-E appear to confer poorer prognosis. IPH2201 blocks the inhibitory function of CD94/NKG2A, thereby unleashing NK and T cells to kill cancer cells, despite expression of HLA-E. IPH2201 enhances NK and T cell killing of a variety of cancer cell types. Hence, IPH2201 may potentially re-establish a broad anti-tumour response mediated by NK and T cells. Anti-NKG2A mAb may also enhance the cytotoxic potential of other therapeutic antibodies. In an ongoing single- and multiple-dose Phase I dose-escalation safety trial in patients with rheumatoid arthritis, IPH2201 appears to have a safe and well-tolerated profile at all doses tested.
- Durvalumab (MEDI4736) is a human monoclonal antibody directed against programmed cell death ligand 1 (PD-L1). Signals from PD-L1 help tumours avoid detection by the immune system. MEDI4736 blocks these signals, countering the tumour’s immune-evading tactics. This antibody is directed against B7-H1, have been shown to block the interaction between B7-H1 and its receptors, PD-1 and CD80 (B7-1). This blockade may help to overcome the immunosuppressive effects of B7-H1 on anti-tumor T cells.
Disease:
Therapeutic
area: Cancer - Oncology
Country:
Trial
details:
Latest
news:
- • On April 18, 2016, Innate Pharma presented data demonstrating enhanced anti-tumor efficacy and survival by combining anti-NKG2A with PD-1/PD-L1 pathway inhibitors in murine models at the American Association for Cancer Research (AACR) Annual Meeting 2016 in New Orleans, Louisiana, USA. The NKG2A checkpoint receptor is expressed on a subset of NK cells. Similar to the PD-1 receptors, NKG2A can also be induced on tumor-infiltrating CD8 T cells. Therefore, PD-1 and NKG2A may both inhibit anti-tumor immune responses in situations where cancers express the ligands of both these checkpoint receptors. Conversely, anti-tumor immune responses might be enhanced by combined NKG2A and PD-1 pathway blockade.
- Poster #2342 reports preclinical data based on an in vivo model of PD-L1 expressing solid tumors. In this model, treatment with either an antibody blocking PD-1 or NKG2A as single agents resulted in modest anti-tumor efficacy. The frequency of tumor-infiltrating NKG2A+ CD8 T cells was increased in anti-PD-1 resistant mice, suggesting that NKG2A is a pathway involved in adaptive PD-1 resistance. Treatment with combination of NKG2A and PD-1 checkpoint inhibitors resulted in significantly enhanced anti-tumor responses. Nearly twice as many mice achieved complete tumor cell regression compared to treatment with anti PD-1 alone.
- AstraZeneca has just initiated a trial, testing the combination of monalizumab, Innate’s first-in-class NKG2A checkpoint inhibitor, and its investigational PD-L1 checkpoint inhibitor, durvalumab,
Is
general: Yes
