The tumour-specific immunogene platform (T-SIGn) has been designed to deliver protein therapeutics selectively to tumor microenvironments following systemic dosing and is moving into Phase 2 clinical testing. Novel antibody fragments have been expressed and validated, including single, bispecific, and biparatopic ScFv, and single and tandem VHH. The functionality of immune checkpoint inhibitors and immune inhibitors will be presented. Perspectives on the expression of combination therapeutics with fragment antibodies and other immune modulatory proteins within the solid tumour microenvironment will be discussed.

Whilst striking success has been seen using CAR T cells to treat leukaemia and other cancers, the majority of solutions are autologous leading to high production costs and logistical challenges. Vg9Vd2-gdT cells are a versatile, non-alloreactive chassis for cellular immunotherapy, possessing potent antibody-dependent cellular cytotoxicity (ADCC) capacity, a tissue-tropic homing profile, and a range of innate tumour-sensing receptors minimizing the likelihood of tumour escape. OPS-gd is a cell therapy platform harnessing these properties, secreting tumour-targeting opsonins and armouring cytokines. OPS-gd cells show equivalent cytotoxicity but superior exhaustion phenotype to CAR-abT cells, recruitment of ADCC-competent bystanders, and in vivo efficacy against patient-derived osteosarcoma.

Affibody molecules are small engineered alternative scaffold affinity proteins that can be site-specifically loaded with cytotoxic drugs to create homogenous conjugates with a desired drug-to-carrier ratio. The presentation will explore the targeting of HER2 and HER3 with affibody-based drug conjugates. It will also describe the impact on biodistribution and in vivo cytotoxic efficacy of drug conjugates loaded with auristatin and maytansine-derived payloads.

The recent approval of the first TCR-based drug represents an exciting advance for cancer immunotherapy. While HLA restriction may potentially limit patient coverage, this may be overcome when the same peptide antigen is presented on multiple HLA alleles. Here, we show that a TCR targeted towards a peptide presented by an HLA allele can be optimised by structure-guided mutations to also bind a second allele with similar affinity and potency.

The potential for future coronavirus outbreaks and ongoing mutations in SARS-CoV-2 highlight the need to broadly target this group of pathogens. Here, we used an epitope-agnostic approach to identify two groups of monoclonal antibodies that target distinct regions of the spike protein and broadly neutralize diverse coronaviruses. Top neutralizers from both antibody classes neutralized all SARS-CoV-2 variants of concern tested including the Omicron subvariant XBB.1.5, inhibited fusion mediated by SARS-CoV-2 spike, and limited disease caused by SARS-CoV-2 in a Syrian hamster model. This two-step approach of isolating rare neutralizing mAbs against cryptic targets is highly relevant for pandemic prevention and the development of therapeutic tools against emerging pathogens.

Identifying genuinely novel targets that have immense therapeutic potential is an increasing challenge across central nervous system diseases. Alchemab addresses this challenge by truly disrupting the target discovery process — simply put, we let the patient select the best targets. We have discovered novel disease-relevant targets through our proprietary platform that searches for protective auto-antibodies in patients who are resistant to disease.

Snake envenomation kills over 100,000 people annually and cripples three times as many. Current treatment relies on animal-derived serum, which, although life-saving presents many drawbacks, including lack of standardisation, a low proportion of neutralising antibodies, and serum sickness from injecting grams of animal protein. Therefore, it is crucial to modernise snakebite treatment. This presentation will show the ongoing efforts in developing the new generation of antivenoms and their associated challenges.

Brain delivery across blood-brain barrier (BBB) is a major hurdle in the development of biological therapeutics for CNS disorders. We developed TXP1 brain shuttle based on anti-TfR1 antibody that can be fused to any therapeutic payload. In monkeys, TXP1 demonstrated ~35-fold improved brain penetration over the control, reaching up to 7.5% brain/plasma ratio. TXP1 showed to be safe and provided brain-specific delivery with no accumulation in other organs and had long-lasting brain PK, essential for efficacious CNS therapies.