A promising immune-stimulating target

For over 100 years, immunotherapy has played a significant role in the treatment of cancer. Immune stimulatory agents such as Toll-like receptor (TLR) agonists, adoptive T cell and natural killer (NK) cell therapies, cytokine-based therapies etc. have gained approval for treatment of various indications. In 1980s, receptor OX-40 was recognized and in 1990s, the cDNA for the OX40 antigen was sequenced. The ligand gained popularity once more in the 21st century as a mono as well as combination therapy for many cancers and is used in both ways now.

OX40 and its ligand OX40L, member of Tumor necrosis factor receptor superfamily, are activated on CD4 and CD8 T cells. OX40 and OX40L interaction act as co-stimulatory signals for T-cell activation. This interaction controls the absolute number of pathogenic or protective effectors T cells that are generated at the peak of the immune response. The augmentation of this interaction enhances antitumor immunity. The interaction between OX40 and OX40L also plays a central role in the development of multiple inflammatory and autoimmune diseases. This makes it fascinating therapeutic candidate for clinical application, especially in cancer and infectious disease area.

Top active companies involved in the OX40 clinical development are Genentech Inc, Pfizer and MedImmune, LLC, which are in process of developing their product candidates through different stages of development. Roche, AstraZeneca and GlaxoSmithKline have candidates, viz. MOXR0916, MEDI6383 and GSK3174998 respectively as combination agents with atezolizumab, durvalumab and pembrolizumab, respectively.

Single nucleotide polymorphisms of OX40L have been identified.  Drug candidates targeting OX-40 are used to treat various cancers. In June 2016, combination  study was examined of the PD-L1 inhibitor atezolizumab (Tecentriq) and the investigational OX40 agonist MOXR0916 which was well tolerated and showed early signs of antitumor activity in solid tumors. Thus, clinical development of OX40 agonists will help to meet unmet future needs in the field of immuno oncology.

Insight by Avita Agarwal
Associate Analyst
DelveInsight Business Research, LLP