While traditional antibodies are limited to cell-surface antigens, our next-generation TCR-mimic (TCRm) antibody platform enables targeting of the vast intracellular proteome, allowing us to address tumour-specific targets such as cancer-testis antigens. This presentation will detail engineering strategies to build next-generation TCRm T cell engagers, designed to achieve a greater therapeutic window in targeting HLA-peptide complexes, and share recent data on how to overcome challenges in treatment of solid tumours.

Immune checkpoint inhibitors have revolutionised cancer treatment for almost every type of malignancy. Despite this success story a high proportion of patients still fail to respond to single agent checkpoint inhibitors, and many responders fail to achieve durable responses. This talk will examine how next-generation strategies are building on this foundation to expand and improve outcomes across a broader range of cancers.

• BCC is the most common skin cancer; high-risk cases, although uncommon, may require morbid surgery with significant functional and cosmetic impact. 
• Neoadjuvant strategies with immunotherapy could reduce tumour burden and improve outcomes.
• Cemiplimab shows efficacy in advanced BCC, while imiquimod and fractional CO2 laser could enhance local immune responses, with potential synergistic effects when combined.
• CEMIQUID is a phase Ib/II trial evaluating neoadjuvant cemiplimab ± imiquimod/laser in resectable high-risk BCC.Phase Ib assesses safety; phase II evaluates efficacy (primary endpoint: 3-year relapse-free survival).
• The study is ongoing in Spain, including translational biomarker analyses.?

Humoral immunity is increasingly recognised as a key determinant of outcome in melanoma. This talk will focus on distinct circulating and intratumoural B cell signatures and antibody isotype profiles we found to be be linked with response and toxicity associated with immune checkpoint inhibitor immunotherapy. Humoral immune signatures conditioned in tumour environments, reveal novel biomarkers for predicting and monitoring immunotherapy efficacy.

Our mission is to transform cancer care by activating the immune system to deliver durable clinical benefit with minimal treatment burden. Aglatimagene besadenovec is a multimodal immunotherapy designed to induce immunogenic tumour cell death and stimulate systemic anti-tumour immunity. This presentation will highlight its mechanism of action, combining localised viral-mediated cytotoxicity with pro-drug activation and immune priming. Clinical and immunological data across solid tumours demonstrates aglatimagene’s therapeutic potential.

TNFR2 is a co-stimulatory receptor that mediates both pro- and anti-inflammatory activities in immune cells. This presentation will examine mechanisms by which ligand-blocking and agonist anti-TNFR2 mAbs induce potent antitumour CD8+ T cell immunity: Treg depletion and myeloid reprogramming versus T cell co-stimulation. Evidence will be presented showing that a first-in-class ligand blocking FcgR-engaging anti-TNFR2 mAb (BI-1808) exhibits both single-agent and anti-PD-1 combination activity in challenging ovarian cancer. The CD4+ and CD8+ T cell-enhancing effects of agonist anti-TNFR2 mAb (BI-1910) highlight potential applications in cell therapy and cancer vaccines.

Cytokine therapies, like IL-2 and IL-21, demonstrate anti-cancer activity through enhanced proliferation, survival, and function of antigen-specific CD8+ T cells, yet off-target effects and rapid clearance have limited their clinical utility. This talk presents clinical updates on AB248 and AB821, CD8-selective cytokines from Asher Bio's cis-targeting platform engineered to precisely activate CD8+ T cells while sparing NK and regulatory T cells — improving both efficacy and safety in solid tumours. AB248 is currently being evaluated in Phase 1 monotherapy, in combination with pembrolizumab, and in combination with tarlatamab, while AB821 is advancing through monotherapy dose escalation.

Single domain antibodies (sdAbs) are versatile building blocks for the design of of bi- and multifunctional- antibody architectures. In this talk, I will present strategies to engineer sdAb-based antibodies that selectively agonise cytokine receptors. I will give examples on several different bi- and multi-specifics that ‘mimic’ the function of given cytokines in the tumour, as well as autoimmune context, and will provide mechanistic insights for the generation of such entities.

IL-2 is a clinically validated immunotherapy. However, toxicity limits its use and despite years of research, the optimal approach to deliver IL-2 has yet to be achieved. AZD6750 applies cis-guiding to deliver a modified IL-2 mutein preferentially to CD8+ T cells. This approach potentially limits the side effects of Aldesleukin, typically attributed to the broad effects of IL-2R signalling, which should result in a safer, more effective IL-2.