Overexpression of a novel apoptosis inhibitor, serine protease inhibitor Kazal (SPIK), has been demonstrated in HCC and other cancer patients. In addition, high levels of SPIK are closely associated with early recurrence in cancer patients following surgical resection. Because recurrence of cancer often implies the immune system’s inability to clear lingering oncogenic cells, early cancer recurrence in patients with high levels of SPIK suggests that the overexpression of SPIK may interfere with the elimination of these oncogenic cells by the immune system.

This is supported by the finding that SPIK can bind to granzyme A (GzmA), a cytolytic granule secreted by CTL and NK cells to kill the target cells during immune-surveillance, and suppress GzmA-induced cytolysis. In addition, cells overexpressing SPIK are tolerant to human T lymphocytes/NK cell-mediated and GzmA-dependent cell lysis. Therefore, suppression of GzmA activity by SPIK may be a factor leading to evasion of cancer cells from immune-killing.

This is supported by the observation that infusion with T lymphocytes which predominantly express GzmA can lower the rate of 3-year tumor recurrence from 77% (57 out of 74) to 59% (45 out of 76) (P<0.01) after surgical resection and delay the initial onset of tumor recurrence. Based on this, ImCare is developing a novel anti-cancer drug which works by restoring the ability of an individual’s immune system to naturally kill oncogenic cells.

This approach could potentially lead to a drug which is far more aggressive and far less toxic than current treatments. Using a high-throughput screening system, we have already identified two compounds, IMB101 and IMB102, which have a potent ability to inhibit SPIK activity in vitro with an IC₅₀ of ~1µM and a CC₅₀ larger than 100µM.

As we continue to analyze and modify our compounds, we move closer to delivering an effective and impactful solution to patients and physicians worldwide.