• Clinical development

PD-L1

PD-1 and its ligand PD-L1 is an important immune regulatory pathway. The interaction between PD-1 and PD-L1 has been reported to negatively regulate the proliferation and cytokine production of T-cells.

PD-L1 expression has been reported on many different tumor cells; accordingly, cancers use it to evade the host immune system. PD-L1 expression has been correlated with poor prognosis in cancer. PD-L1 expression on tumor cells has been further correlated with increased tumor aggressiveness and increased risk of death for a number of solid cancers, including ovarian cancer and pancreatic cancer. In addition, surface expression of PD-L1 on cancer cells has been described in several hematological cancers.

PD-L1-reactive CTLs are readily isolated from the peripheral blood of cancer patients and to a lesser extent from the blood of healthy donors.

Thus, PD-L1 may serve as a widely applicable target for immunotherapeutic strategies.

IO101

IO101 is a peptide vaccine encompassing an HLA-A2-restricted, 9 amino acid IDO-derived CD8+ T-cell epitope. IO101 is currently in phase II clinical trial.

A first-in-man clinical phase I vaccination trial using IO101 was conducted. The study comprised 15 HLA-A2+ patients with advanced NSCLC who were vaccinated with IO101 in Montanide adjuvant following pre-treatment with topical Imiquimod (Aldara® Cream). The vaccine was well tolerated with manageable side effects and no CTCAE grade 3/4 toxicities.

One patient obtained an objective partial response after demonstrating continuous regression of liver metastases on vaccine treatment for 1 year.

Presently a small phase II study is ongoing in melanoma patients. In this study, IO101 together with an A2 Survivin peptide is used for vaccination in combination with temozolomide chemotherapy treatment.

More information can be found in this recent publication: Long-lasting disease stabilization in the absence of toxicity in metastatic lung cancer patients vaccinated with an epitope derived from indoleamine 2,3 dioxygenase