今月ロンドンで開催されたGlobal EngageのImmuno-Oncology Research&Technology Series Meetingでは、免疫系を利用してがんと戦う方法に関する興味深いインサイトが公開されました。 この会議は、細胞療法、新規抗体、ネオ抗原などにおける最先端の開発をカバーする5つのセッションで構成されていました。 Cortellisチームがまとめたハイライトの一部を以下に示します。

ImCheck’s ICT-01 gamma-delta T-cell activator has preclinical efficacy

ImCheck Therapeutics’ CSO, Rene Hoet, discussed the preclinical development of ICT-01, a BTN3A-activating antibody that stimulates gamma-9-delta-2 (g9d2) T-cells, and which is due to enter the clinic in early 2020. ICT-01 was shown to induce the trafficking of g9d2 T-cells in an organoid model of ovarian cancer (SKOV3 and HFF2). In murine models of acute myeloid leukemia (AML) and ovarian cancer, the therapy delayed tumor growth and increased survival. Safety and target-engagement studies were conducted in cynomolgus monkeys; BTN3A was rapidly occupied after ICT-01 injection. The therapy had typical IgG-like pharmacokinetics, with a half-life of 9 days, and had a specific effect on gd T-cells but no other T-cell subsets. The increase in cytokine levels was only marginal, and there was no adverse finding in clinical signs, including bodyweight, clinical pathology and anatomical pathology. Clinical development of ICT-01 as a monotherapy and in combination with programmed cell death protein 1 (PD-1) blockade is to start in Europe in 2020, followed by expansion to the US.

Kymab’s ICOS binder KY-1044 utilizes dual mechanism of action

Sonia Quaratino, CMO of Kymab, discussed the mechanism of action of Kymab’s ICOS binding agent KY-1044. The drug has a dual mechanism of action, which is expected to increase antitumor efficacy. It depletes ICOS-high-expressing regulatory T-cells (Treg), but also activates lower-ICOS-expressing T-effector cells (Teff). Studies in cynomolgus monkeys confirmed that the drug depleted ICOS-high T-cells. In murine A20 and CT26 tumor models, KY-1044 demonstrated efficacy both as a monotherapy and in combination with anti-PD-(ligand)L1 antibodies. Anti-PD-L1, rather than anti-PD-1, antibodies are the partner of choice for KY-1044. In murine models, a 70% cure rate was seen with the KY-1044/anti-PD-L1 combination, compared with a 10% cure rate for the KY-1044/anti-PD-1 one.

PACT Pharma develops personalized TCR-based T-cell therapy

The CEO of PACT Pharma, Alex Franzusoff, reported on the company’s development of neoTCR-T cells, a personalized neoantigen/neoepitope-targeted T-cell therapy in which a patient’s native tumor-specific TCRs are identified then engineered ex vivo into autologous T-cells in order to provide a personalized tumor-targeting therapy. PACT first predicted TCR targets, comprising an HLA type and a neoantigen/neoepitope, which were assembled into a platform against which patient blood samples were screened for responsive T-cells. In virtually every patient studied, regardless of tumor type or tumor-mutational burden, tumor-specific T-cells were found. The TCRs from these tumor-responsive cells were then engineered into other CD4 and CD8 T-cells from the patient, overwriting the existing TCR, and are reintroduced. T-cells of a memory stem cell type are used as using T effector cells would create a product with only a transient effect. The process has demonstrated tumor eradication in mice and is currently being assessed in the PACT-0101 phase Ia/Ib trial (NCT03970382). The first clinical data are expected from this study in the first half of 2020.

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