Affimer® biotherapeutics: The next generation of cancer therapies

This week we are attending PEGS Europe, the premier protein and antibody engineering summit, which is taking place 14-16 November in Lisbon, Portugal. During the Congress, we will be presenting a poster describing our Affimer® technology platform and its potential applications.

Avacta’s proprietary Affimer® technology provides a platform for a new class of protein biotherapeutics with high target selectivity and specificity.  Affimer® proteins (15kDa) can be formatted into multi-specific proteins containing multiple Affimer® units, with further options to modulate PK properties or fuse to proteins, including cytokines for targeted delivery. Additionally, their size, design flexibility and thermostability offer opportunities to deliver radionuclides or other toxic payloads to tumours.

Affimer® molecules offer many advantages over traditional monoclonal antibodies, include their small size, increased stability, specificity and ability to bind difficult drug targets such as GPCR’s. These characteristics are particularly advantageous when targeting solid tumours, which can be hard to access for larger therapeutic molecules such as antibodies.

At Avacta, we have developed a highly specific Affimer® which targets programmed cell death ligand 1 (PD-L1), a protein that stops our immune cells attacking and destroying tumour cells, by effectively masking the tumour from the human immune system. By inhibiting PD-L1, the immune system remains active and can continue to fight and destroy the tumour.

Antibody-based anti-PD-L1 therapies have achieved great success in the past decade, but only a subset of patients will respond to the therapy, of which many go on to develop resistance overtime. Both these limitations of the PD-L1 targeted therapies are associated with the quality and duration of the body’s immune response. To combat resistance and an inactive immune system, research in recent years has focused on targeted stimulation of the immune response at the tumour site. This can be achieved by combining anti-PD-L1 agents with other immuno-modulating agents, such as cytokines.

Cytokines are small cell-signalling proteins that are involved in the development and activity of the immune system. When produced and released by cells, they can regulate the immune response and induce inflammation in the local microenvironment. When combined with anti-PD-L1 agents and targeted to a tumour, cytokines can induce a lasting response at the tumour site and ensure the immune system remains active, killing cancer cells. We have taken advantage of the flexibility of the Affimer® platform to deliver both an anti-PD-L1 agent and a cytokine at the tumour site, simultaneously. This is made possible by the multiple formatting configurations that are possible, whereby individual Affimer® molecules can be combined to form complexes that target multiple proteins at once or carry agents that can modulate the tumour micro-environment.

Our lead Affimer® AVA032 is an anti-PD-L1 Affimer® fused to the pro-inflammatory cytokine interleukin 15 (IL-15) and has dual activity that works to reverse the immunosuppressive tumour micro-environment, inducing a lasting immune response aimed at stimulating a patient’s immune system to destroy cancer cells. By boosting the immune response, this combination treatment produces a sustained immune response and maximising response to immuno-oncology therapy.

  • Download the poster ‘Affimer® biotherapeutics: Next generation platform for cancer therapies’ here.