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Research Collaboration Seeks to Optimise Dual-Targeted NK Cell Therapy Against Acute Myeloid Leukaemia

Phacilitate
26 May 2021
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A new research agreement, funded by ONK Therapeutics (Galway, Ireland) and based at the National University of Ireland, Galway (NUI Galway), seeks to support the development and optimisation of a dual-targeted NK cell therapy candidate for acute myeloid leukaemia (AML).

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AML is reported to be the most common form of acute leukaemia in adults, with an estimated ~21,000 diagnoses in the US and ~18,000 in Europe each year. With the lowest survival rate among leukaemia types, there is a high demand for therapeutics that may offer long term control and treatment for the disease.

ONK Therapeutics – a company focussed on the optimisation of next generation, off-the-shelf, dual-targeted NK cell therapies – has therefore announced a research agreement with NUI Galway to support the optimization of ONK Therapeutics’ own dual-targeted NK cell therapy program for AML treatment, ONKT104. 

NUI Galway will provide unique access to expertise in cancer cell microenvironment evaluation in AML, as well as the targeting of AML stem cells in bone marrow microenvironment-mimicking models, as Michael O’Dwyer, ONK Therapeutics’ founder and CSO explained:  

“Alongside our in-house research, the project team at NUI Galway will explore construct design, as well as the potential added benefit of certain gene edits to enhance NK cell cytotoxicity, cytokine production and persistence in the context of AML strengthening our ONKT104 program. The aim is to select an optimized candidate to take forward into clinical development as a treatment for patients with relapsed/refractory AML.”

The news follows ONK Therapeutics’ December 2020 announcement of three exclusive option license agreements, which included a humanized scFv targeting a novel tumor-specific MUC1 glycopeptide epitope licensed from Glycotope GmbH (Berlin, Germany), a CCR7 homing receptor licensed from the National Institute of Health (MD, USA) and a humanized scFv targeting CLEC12A (or CLL-1) licensed from Cellerant Therapeutics (CA, USA)

The latter is the option license agreement of interest in this case, as it is associated with the dual-targeted NK cell therapy – ONKT104 – alongside ONK Therapeutics’ proprietary high-affinity TRAIL variant, targeting death receptor 4 (DR4). 

 ONK Therapeutics reports that pre-clinical research has indicated a monoclonal antibody therapy targeting CLL-1 may be successful against AML cells and that a CLL-1 CAR-T cell model has shown positive results after recently entering the clinic. However, ONK Therapeutics believes an off-the-shelf, dual-targeted NK cell therapy approach could be more effective in simplifying the process and reducing the time to treatment for each patient. 

 In addition to targeting CLL-1, the project will further evaluate multi-targeted approaches, combining targeting of other stem cell antigens associated with leukaemia, as Dr Eva Szegedi, Lecturer in Biochemistry at NUI Galway and Head of the Blood Cancer Network Ireland – who will be supervising the research agreement – concluded:

“The project will evaluate different constructs that may be able to achieve synergistic killing of cancer cells and reduce the emergence of disease resistance. These include the co-expression of CARs targeting other AML antigens, in addition to CLL-1, such as CD96, TIM3 and CD38 alongside the TRAIL variant.”

Source: ONK Therapeutics press release

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