UniTope & TraCR is a universal detection system for 3S recombinant TCRs in TCR-T cell therapies. The integrated epitope (UniTope) eliminates the need for extraneous gene tags, providing an unequivocal identity marker. The system facilitates efficient in vitro and ex vivo monitoring via a single TraCR antibody. UniTope integration preserves TCR structural and functional integrity, streamlining identification, quantification, and quality control of TCR-T cells expressing 3S rTCRs.

Vγ9Vd2 T cells stand in between the innate- and adaptive-immune responses and constitute a powerful immune effector-cell population amenable for cancer treatment. Bispecific T cell engagers (bsTCEs) binding the Vd2 T cell receptor (TCR) and tumor-associated antigens (TAA) effectively trigger Vγ9Vd2 T cells to lyse multiple type cancer cells, while sparing normal cells. Currently, a PSMA-targeting bsTCE is being evaluated in a phase 1/2a clinical trial in prostate cancer patients.

B cells, critical to autoimmunity, have been identified as potential therapeutic targets in the treatment of autoimmune disorders. Our next-generation CUE-500 series Immuno-STATs are uniquely engineered Fc fusion molecules that redirect and activate cytotoxic T cells, targeting pathogenic B cells. Leveraging clinical efficacy and safety of our CUE-100 series Immuno-STATs, our novel autoimmune platform enables the redirection of Immuno-STATs towards pathogenic B cell depletion for the treatment of autoimmune diseases.

Mucosal Associated Invariant T cells (MAITs) are an abundant, tissue/tumor resident, subset of cytotoxic non-conventional T cells. Bi-specific antibody-mediated redirection of MAIT cells leads to the elimination of cancer cells with a potency identical to that of classical CD3e T cell engagers. However, in contrast to CD3e engagers, MAIT engagers do not cause widespread cytokine release and regulatory T cell activation and afford a large therapeutic window, favouring the treatment of solid tumors. Tumor resident MAIT cells are able to eliminate autologous tumor cells in a MAIT-engager mediated manner and can infiltrate and kill tumor cells in patient derived 3D models of cancer.

A wide range of tumour types can be recognized by ?9d2T cells in in vitro experiments, however the low affinity of ?9d2TCR for their tumour antigens, the phosphoantigen dependent BTN2A1-BTN3A complex, results in poor clinical outcomes. Using our recently developed ?9d2TCR-antiCD3 TCE to screen for potency enhancing mutations resulted in affinity enhanced ?9d2TCRs with significantly enhanced tumour control, both in vitro and in vivo, paving the way for the next generation of ?9d2TCR-based immunotherapies.

TNFR2 is a co-stimulatory receptor mediating pro- and anti-inflammatory activity in immune cells. This talk will discuss mechanisms by which anti-TNFR2 mAbs regress large inflamed tumours and synergize with anti-PD-1 to induce cures and robust antitumor CD8+ T cell immunity in syngeneic mouse tumour models. Compelling evidence that the first-in-class anti-TNFR2 mAb (BI-1808) can be safely administered and has single-agent anti-tumour activity in difficult-to-treat cancer, e.g., GIST, will also be shared.

While agonistic antibodies represent promising novel therapeutic avenues to treat human diseases, the lack of an effective identification process has significantly hampered their discovery. Using a combination of experimental and computational approaches, we were able to generate bispecific agonist antibodies that activate IL-18 receptors directly, inducing IFN, while sparing myeloid cells, avoiding a tolerability issue associated with IL-18 and its muteins, thus offering an activity driven towards anti-tumour effects.

Neoantigens are emerging as the main determinants of tumour immunogenicity and efficacy of immune checkpoint blockade, but their presence does not guarantee durable responses in patients with cancer. Here we developed a comprehensive structure-function approach to identify the main characteristics of neoantigens in melanoma and acute myeloid leukemia, originating from somatic mutations and from post-translational modifications, affecting the outcome of checkpoint blockade.

Cytokines are proteins that are capable of potently modulating the activity of the immune system and certain cytokines (e.g., interleukin-2, interferon-alfa, tumour necrosis factor) have gained a marketing authorization for cancer therapy. The fusion of cytokines to tumour-homing antibodies has been shown to potently increase the therapeutic index of the cytokine payload in animal models of cancer. In this lecture, I will present examples of potent therapeutic activity mediated by certain antibody-cytokine fusions, developed by Philogen, which are now being studied in pivotal clinical trials

Masking cytokine technologies with enzymatic cleavable linkers allows activity on-demand at the right site but suffers from enzyme selectivity. Cis-delivery cytokine technologies allow redirection of activity on the right cells but require potent cytokine attenuation for optimal cell selectivity. OSE-Cytomask is a novel Cis-Demasking cytokine technology avoiding cytokine attenuation and cleavable linkers to unmask cytokines on-demand on selective immune cell subsets expressing the appropriate surface antigen.

Antibody-cytokine conjugates leverage orthogonal mechanisms-of-action (MoA) in one molecule to induce potent antitumour immune responses. At Bright Peak, we generate immunocytokines through site-specific chemical conjugation of cytokine to “off-the-shelf” human IgG antibodies. During the talk, I will focus on our PD-1-targeting conjugates and share compelling preclinical data supporting the future development of BPT567, a PD1-IL18 immunocytokine.