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With the start of the new academic year, we are delighted to kick-start this year's ECRN seminars by welcoming Dr Jun Ishihara, Lecturer in Bioengineering at Imperial College London. Join us on Microsoft Teams from 1 – 2 pm, Tuesday 25th October for this month’s seminar, where Dr Ishihara will be presenting his work on cancer immunotherapeutics:
Molecular Engineering to Develop Novel Vascular-Targeted and Masked Cancer Immunotherapeutics
Abstract: Peripheral toxicity limits the use of systemic cytokine therapy for solid tumours in clinical practice. The conjugation of anti-tumour cytokines such as IL-12 to a Collagen-Binding Domain (CBD) allows for targeted IL-12 delivery into the highly collagenous tumour stroma via intravenous injection. We took further engineering approaches to increase its tolerability and efficacy in clinical practice. Here, through a masking technique, we solved IL-12 toxicity by preventing its interaction with the IL-12 receptor whilst in the periphery. The mask is fused to the p35 subunit of IL-12 through a cleavable linker, which is designed to be an ideal substrate for tumour-specific proteases. Tumours rely on the over expression of such proteases for degradation of the extra-cellular matrix and therefore metastasis. The proteases in the tumour cleave the linker once the masked IL12 penetrates the tumour stroma, thereby allowing IL-12 to engage with its receptor. IL-12 consequently primes the innate and adaptive immune system exclusively inside the tumour stroma rendering the tumour ‘immunologically hot’. In several solid tumour models the therapeutic effects of masked IL-12 were similar to its unmasked form, yet its toxicity was significantly suppressed.
As with our recent flash talks, we will drive to make active discussion a key part of each seminar with the aim of making connections and building collaborations with researchers across the network and the wider London advanced therapeutics research community.
Microsoft Teams meeting. Click here to join the meeting.