Diverse Approaches in Immuno-Oncology: A Review of the Research & Technology Series
Posted 13th November 2019 by Joshua Sewell
This blog was published on Clarivate’s Cortellis blog. It is reproduced here with their kind permission.
A fascinating range of insights into the ways in which the immune system can be harnessed to fight cancer was provided by Global Engage’s Immuno-Oncology Research & Technology Series meeting held in October in London. The conference comprised five concurrent tracks covering cutting-edge developments in fields such as cell therapies, novel antibodies and neoantigens. Some of the highlights tracked by the Cortellis team are presented below.
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 leukaemia (AML) and ovarian cancer, the therapy delayed tumour 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 tumour 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 tumour-specific TCRs are identified then engineered ex vivo into autologous T-cells in order to provide a personalized tumour-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 tumour type or tumour-mutational burden, tumour-specific T-cells were found. The TCRs from these tumour-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 tumour 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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