Induction of immunogenic cell death (ICD) in cancer has been proposed as a promising strategy to elicit potent adaptive immune responses against tumor-associated antigens, potentially overcoming the limited efficacy of immunotherapy in some patients and tumor types. Since type I interferon (IFN) is a key modulator of ICD in antitumor responses, researchers at the University of California, San Diego are investigating how to expand the IFN effect to promote ICD responses in cancer cells.
While immune checkpoint inhibitors have revolutionized oncology, still only 20-30% of patients respond to PD-1/PD-L1 antibody monotherapy. This can be due to a failure of T cells to recognize “cold” tumors (low T-cell infiltrates).
TANK-binding kinase 1 (TBK1) is a multifunctional serine/threonine kinase with an established role coordinating innate immune responses, and it has been previously identified as a candidate immune evasion gene. Additionally, disrupting TBK1 signaling has shown potential for enhancing response to immunotherapy with immune checkpoint blockade (ICB) in murine tumor models.
Immunotherapy, a treatment that increases the survival of cancer patients to the point of remission of the disease, can also have the opposite effect. In some patients, immune checkpoint blockade accelerates cancer. Now, researchers at the University of Michigan Medical School have discovered that the answer to this hyperprogressive disease (HPD) lies in the interconnection of the molecular pathways of interferon signaling (IFNγ), fibroblast growth factor 2 (FGF2) and the β-catenin protein.
The alpha chain of the IL-3 receptor, CD123, is frequently overexpressed in acute myeloid leukemia (AML) and is considered an attractive target in the treatment of this disease. However, cytotoxic antibodies or T-cell engagers targeting CD123 have shown insufficient clinical efficacy or safety, confirming the need for alternative targeted approaches.
Immunos Therapeutics AG has received full ethical institutional approval from the Human Research Ethics Committee (HREC) and regulatory approval from the Australian Therapeutic Goods Administration (TGA) to conduct a phase I trial of its lead program IOS-1002 in Australia.