From June 20-22, 2023, Cambridge Healthtech Institute hosted the seventh annual Immuno-Oncology Summit Europe in London. DDW’s Megan Thomas shares highlights from the event programmes.
This year’s summit was made up of conference programmes, which included: Modulating the Tumour Microenvironment; Next-Generation Cell-Based Immunotherapies; Bispecific and Multi-Specific Antibody Therapeutics, and Gamma Delta Immunotherapy.
In the Modulating Tumour Microenvironment programme, experts took a deeper look at the results we are seeing from emerging immunotherapies such as immune checkpoint blockade and chimeric antigen receptor T cells (CAR Ts), and also discussed advances in our understanding of and strategies to modulate the tumour microenvironment. Having introduced the session with his Chairperson’s remarks, Dr Russell Jenkins, a Faculty Member at the Center for Cancer Research at Massachusetts General Hospital, then spoke in depth about targeting TBK1 to overcome resistance to cancer immunotherapy.
In the Next-Generation Cell-Based Immunotherapies programme, discussed the challenges associated when initial good responses to T cell therapies are followed by rapid relapse owing to tumour-related mutations and evasion mechanisms put out by the tumour, and explored the next wave in CAR T cell therapies, advances in T cell engineering, updates on CAR-M, CAR-NK as well as clinical updates on TCRs and TILs. Dr Agapitos Patakas, CSO, Research & Development, Antibody Analytics, presented in this track on a customisable cell line platform for in vitro assessment of safety and efficacy of immune cell-directed therapies.
The Bispecific and Multi-Specific Antibody Therapeutics programme showcased preclinical, translational, and clinical studies on using bispecific antibodies for dual blockade of checkpoint targets, T-cell-redirecting bispecific biologics, overcoming T-cell exhaustion, as well as strategies to improve efficacy and reduce toxicity, and engineer the next generation of bi- and multi-specific biologics. A highlight included a presentation by Dr Anette Sundstedt, Principal Scientist, Alligator Bioscience AB, on Neo-X-Prime, a platform based on bispecific conditional CD40 agonistic antibodies that target TAAs expressed at high densities, where the lead program, ATOR-4066, targets CD40 and CEA.
The programme on the topic of Gamma Delta Immunotherapy explored a range of ways to take advantage of Gamma-delta T cell properties, as well as ways to enhance them for effective treatment. This included broad antigen recognition, multivalent responses and the lack of MHC restrictions. Dr Aude De Gassart, Director, Preclinical Research, Imcheck Therapeutics, took a deep dive into the EVICTION-2 clinical trial, which is combining ImmunoCytokines and ICT1 to expand endogenous Gamma9Delta2 T Cells.
A feature of this year’s event were in-person only breakout rooms, where attendees could engage informally with experts in a range of immune-oncological topics, aided by a moderator. On the topic of Strategies for Engineering of Gamma Delta T Cell Constructs, Dr Mariolina Salio, Director, Experimental Immunology, Immunocore, and Dr H Trent Spencer, President, Expression Therapeutics, engaged with ideas and experiences relating to the use of gene editing technology, engineering of gamma delta-based TCRs, and the creation of gamma delta fusion constructs.
Meanwhile, Dr Faith Howard, Early Career Researcher, Oncology & Metabolism, University of Sheffield, facilitated a breakout discussion on inflaming the TME using oncolytic viruses, which answered the question of whether viruses ‘“go it alone’“ or are an ‘“the opening act’“, as well as compared intravenous and intratumoural delivery for targeted intravenous delivery of cancer-killing viruses as a viable treatment strategy for hard-to-reach, immunologically cold tumours. This session also covered the platforms for oncolytic virus delivery beyond liposomes and clinical translation of nanomedicines.
Over on the Next-Generation Cell-Based Immunotherapies programme, Dr Paul Neeson, Associate Professor, Cancer Immunology Research, Peter MacCallum Cancer Centre, led a breakout session on novel engineered CAR T cells for solid tumours. This covered features of the TME which are hostile to CAR T cell efficacy, strategies for engineering CARs to address the solid tumour TME hurdles, as well as combination treatments with novel CARs such as chemotherapy, radiotherapy, and oncolytic virus.
In terms of the Bispecific and Multi-Specific Antibody Therapeutics programme, Dr Miguel Gaspar, Director, AstraZeneca, covered a breakout on T Cell redirection with bispecific antibodies, both in terms of strategies and clinical examples. This was centred around pre-clinical models (in vitro and in vivo) to support discovery and development, re-entering the fray with costimulatory agonists, and clinical development strategies for combinations with immune cell engagers.
The findings presented by Dr Christian Klein, Head of Oncology Programs and Department Head of Cancer Immunotherapy Discovery, Roche Innovation Center Zurich, Roche Pharma Research & Early Development, pRED, bear major implications for the development of the next-generation of IL-2 therapies. In his presentation, he focused on overcoming the limitations of aldesleukin and biased IL-2Rbg agonists by PD-1 cis-targeting of IL2v with the PD-IL2v immunocytokine.
Also noteworthy were the findings presented by Dr Barbara Loesch, Head, Technology & Innovation, Medigene AG, on how the PD1-41BB switch receptor technology added to TCR Ts further enhances antitumour activity in vitro and in vivo compared to TCR alone.
Elsewhere at the conference, Dr Theresa A Deisher, President & CSO, R&D, AVM Biotechnology, presented on induction and mobilisation of endogenous bispecific gamma delta TCR+ invariant TCR+ natural killer T cell-like cells in Non-Hodgkin’s lymphoma and solid tumour patients. Preclinically, activity has been demonstrated against autoreactive T/B cells, immune-resistant lymphoma, xenografted human T-ALL, melanoma, and multiple myeloma, and AVM0703 is also effective as neoadjuvant before chemoimmunotherapy or cell transplant.
As for poster highlights, Dr Francesca Rucci, Senior Principal Scientist, Novartis Institutes for BioMedical Research, shared insight into the first-in-class anti-CD19, anti-CD3, anti-CD2 trispecific antibody (PIT565) for the treatment of B cell malignancies.