IL-12 inhibitors Pipeline Insights
- Interleukin-12 (IL-12) is a heterodimeric protein that consists of IL12, IL23, IL27, and IL35 cytokines, first recovered from EBV-transformed B cell lines.
- The properties of multifunctional cytokine bridge innate and adaptive immunity, acting as a key regulator of cell-mediated immune responses through the induction of T helper 1 differentiation.
- By promoting IFN-γ production, proliferation, and cytolytic activity of natural killer and T cells, IL-12 induces cellular immunity. In addition, IL-12 induces an antiangiogenic program mediated by IFN-γ–inducible genes and by lymphocyte-endothelial cell cross-talk.
- The immunomodulating and antiangiogenic functions of IL-12 have provided the rationale for exploiting this cytokine as an anticancer agent. Interleukin-12 (IL-12) is recognized as a key regulator of adaptive type 1, cell-mediated immunity, the critical pathway involved in protection against neoplasia and many viruses.
- Antibodies that inhibit IL-12/23 or IL-23 are key treatment options for patients with psoriasis. Ustekinumab was one of the first agents to offer an alternative mechanism for the treatment of psoriasis and psoriatic arthritis, by blocking the IL12 and IL23 cytokines. IL-12 and IL-23 also play a key role in immune responses to infections and tumors.
- The newly-developed recombinant immune-cytokine, IL12-SS1 (Fv), was produced in insect cells using a baculovirus-insect cell expression system. IL12-SS1 (Fv) is the first reported immune-cytokine to mesothelin-positive tumors and may be an attractive addition to mesothelin-targeted cancer therapies. The recombinant immune-cytokine produced in baculovirus-insect cell expression system is as biologically active as IL12 alone.
- IL12 invokes an antitumor response in a murine model of malignant mesothelioma. IL12 has displays robust antitumor and anti-metastatic activity in preclinical studies.
- Clinical trials in patients with cancer have disclosed optimistic therapeutic activities, but have also shown that recombinant human IL12 is highly toxic to humans. Majority of studies are going on are in phase 1 development stages of clinical trials when compared to phase 2 and phase 3 studies. And only a few studies are going on in phase 2 and phase 3 clinical trials.
- Thus new therapeutics must be improved that will add to the introduction of new drug candidates to market. A growing body of information from clinical trials, cohort studies, post-marketing reports, genetic studies, and animal models provides insights into the potential biological relationships between IL-12 inhibition and malignancies.
