The immune system has already provided a number of potent strategies for treating cancers that are already impacting clinic, which in turn has stimulated a great deal of research into developing further cancer immunotherapies. There remain, however, a number of significant challenges, yet to be overcome, such as their range of efficacy among cancer patients and often quite intolerable toxicities associated with many immuno-oncology treatments. Furthermore, given the large volume of ongoing clinical trials with various combinations of existing cancer immunotherapies, it can be easy to overlook ground-breaking research into the future of immuno-oncology.

At the 5th annual Immuno-Oncology Summit Europe 2020, from 9-12 March, in London, UK, there will be a wealth of presentations, discussions, and information sharing on the next generation of cancer immunotherapies that have seen significant success in both in vivo and in vitro preclinical trials and are now entering the clinic. Not only addressing challenges of efficacy and safety but also developing new therapies with novel mechanisms for treating a range of cancers all the while broadening the oncologist’s toolkit. See below a selection of such talks and be sure to click on the links to see the full agendas.

FEATURED PRESENTATION: Stress-Induced Post-Translational Modifications (siPTMs) as Targets for Cancer Vaccines

Lindy Durrant, Ph.D., Professor of Cancer Immunotherapy, University of Nottingham; CSO, Scancell Ltd.

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Citrullination is a widely expressed, novel, stress-induced post-translational modification that is a potent target for cancer vaccines. There is a repertoire of cytotoxic CD4 T cells in mice and humans that recognizes citrullinated epitopes. Tumors over-express PAD enzymes. Inflammation and stress induce high levels of autophagy and MHC-II presentation of citrullinated epitopes on tumors. Citrullinated peptides demonstrate potent anti-tumor immunity with no associated toxicity and will shortly enter the clinic.

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Next-Generation Bispecifics for Cancer Immunotherapy

Michelle Morrow, Ph.D., Vice President, Preclinical Translational Pharmacology, F-star

The use of bispecific antibodies can potentially modulate anti-tumor immune responses. Bispecific antibodies: an attractive alternative to cancer treatment combinations. F-star’s approach to creating bispecific mAb². In vitro and in vivo efficacy of F-star bispecific antibodies targeting oncology pathways observed in preclinical studies.

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Antibody-Drug Conjugate and Oncolytic Virus-Based IO Combinations: Different Modalities – Common Themes

Philipp Müller, Ph.D., Senior Principal Scientist, Cancer Immunology & Immune Modulation, Boehringer Ingelheim Pharma GmbH & Co. KG

Despite the clinical breakthroughs achieved with checkpoint blockade, the overall proportion of patients experiencing durable responses remains relatively small. Therefore, the real promise for most cancer patients lies in complementary combination therapies, combining checkpoint blockade with the immune-promoting/supporting properties of other therapeutic modalities, which help breach physical barriers, overcome immunosuppression and improve immune cell infiltration in tumors. This talk will compare and highlight two of the latter categories: Antibody-drug conjugates and oncolytic viruses.

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Novel Immune-Cell Targeted IL2v to Deliver IL-2R Signaling to Tumor Reactive T Cells via PD-1 whilst Blocking the PD-1 Pathway

Laura Codarri Deak, Ph.D., Principal Scientist, Cancer Immunotherapy, Roche Pharmaceutical Research, and Early Development

Interleukin-2 has been the first effective cancer immunotherapy to treat metastatic melanoma and renal cell carcinoma, although only a fraction of patients benefits, the anti-tumor responses are complete and durable. Unfortunately, IL-2 is toxic and detrimentally expands regulatory T cells.

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Developing Personalized Neoantigen Cancer Vaccines to Target Solid Tumors

Karoline Schjetne, Ph.D., Vice President Scientific Affairs, Vaccibody

Vaccibody is a clinical-stage biotech company dedicated to the discovery and development of novel immunotherapies. Vaccibody is a leader in the rapidly developing field of individualized cancer neoantigen vaccines and is using the Vaccibody technology to generate best-in-class therapeutics to treat cancers with a high unmet medical need. The talk will focus on preclinical data underlining the superior vaccine technology and present clinical updates on the Phase I/IIa VB10.NEO vaccine trial VB N-01.

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New Broadly Expressed Cancer Targets from Successful TIL Therapy

Andrew Sewell, Ph.D., Distinguished Research Professor and Wellcome Trust Senior Investigator, Infection & Immunity, Cardiff University School of Medicine

Over 20% of melanoma patients that have been refractory to other treatments undergo complete lasting remission after adoptive cell transfer of tumor-infiltrating lymphocytes (TILs). Dissection of these extraordinary successes by examining the dominant tumor-reactive T cell clonotypes in the TIL infusion product and patient blood after ‘cure’ has revealed some surprising, exciting new HLA-restricted and non-HLA restricted T cell targets that are expressed by many other tumor types.

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CARs and Armored CARs

Renier Brentjens, MD, Ph.D., Director, Cellular Therapeutics Center, Memorial Sloan-Kettering Cancer Center; Professor, Pharmacology, Weill Cornell Graduate School of Medical Sciences

Based on currently updated clinical outcomes, we have achieved >85% CR rates in adult patients with relapsed B-ALL treated with CD19 targeted CAR T cells which far exceed historical expectations. Further, by deep sequencing analysis, most treated patients were MRD- after CAR T cell therapy. Significantly, remissions were observed in both patients with overt morphological residual disease at the time of therapy as well as in patients with only residual MRD+ disease. To this end, we will present novel data on the next generation of CAR T cells, termed “armored CARs” further genetically designed to overcome an immune-suppressive tumor microenvironment through further genetic modification of CAR T cells.

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Advances in Immunotherapy: Maximizing T Cell Responses with Tumor Antigen Directed Bispecific Antibodies and Co-Stimulation

Maria Karasarides, Ph.D., Executive Director, ImmunoOncology, Regeneron Pharmaceuticals

Immunotherapy has advanced as an integral cancer treatment modality primarily from the survival outcomes observed from checkpoint inhibition (α-CTLA-4, α-PD-1, α-PD-L1). While the benefits from checkpoint inhibition are evident, long term survival is enjoyed by only a small proportion of cancer patients harboring immune-responsive tumors. In this talk we will (1) review the long term survival outcomes provided by checkpoint inhibition (2) discuss immunotherapy combination strategies and outcomes to date (3) explore potential of achieving maximal T cell responses through the use of tumor antigen directed bispecific antibodies and co-stimulation to address the unmet need remaining for cancer patients with immune-response and non-responsive tumors.

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