Emerging cell- and protein-based cancer immunotherapies are a game-changer for treating cancers. Currently, medical science is on the cusp of delivering on the promise of making cancer a manageable disease. But the impediments to commercializing cancer immunotherapies are substantial.
In this eBook, author Angelo DePalma dives into the economic and processing problems that the industry faces in developing these life-changing therapies. He examines protein immunotherapies and cell-based immunotherapies that have made it to the clinic, providing an overview of the current state of the industry in delivering these biotherapeutics. DePalma also gets into the manufacturing strategies involved and how companies are approaching product and process development.
Issues In Protein Immunotherapy
Immunotherapy Squared: Bavituximab, a monoclonal antibody from Peregrine Pharmaceuticals (Tustin, CA), is a classic protein immunotherapy targeting phosphatidylserine (PS), a novel immune system checkpoint. PS exists on the inside membrane layer of every cell, but it externalizes when cells die. “In circulation, PS signals the immune system to engulf dying cells,” explains Steve King, Peregrine’s chief executive officer (CEO). PS also limits the immune response. As tumors proliferate, they often outgrow their blood supply so that many cells die, sending more PS into circulation. Tumors also release microparticles containing PS, ultimately suppressing immune response to the tumor by keeping the host’s immune system busy fighting particles and dead cells.
Peregrine’s collaboration with AstraZeneca for clinical development could be described as “immunotherapy squared.” Bavituximab’s presumed mode of action is to block immunosuppression while activating a tumor-killing T-cell immune response. AstraZeneca’s investigational anti-PD-L1 immune checkpoint inhibitor, durvalumab, targets the programmed cell death ligand PD-L1, which helps tumors go undetected by the immune system. Both companies believe that combining the enhanced T-cell–mediated antitumor activity with a checkpoint inhibitor will extend the ability of tumor-specific T-cells to attack cancerous cells.
Like many small biopharmaceutical companies with a promising pipeline product, Peregrine chooses to emphasize clinical development over manufacturing or process development, confident that if bavituximab succeeds in the clinic, then CoG issues will resolve themselves. “Our process flexibility assures that we could duplicate the entire facility and all its infrastructure in an open warehouse space almost anywhere,” King affirms. “We built the current facility with the idea of supporting production lots early in commercialization. At that point you have substantial revenue, so all your manufacturing avenues open up. And the risk of sticking with the same systems, at the same scale, from a comparability standpoint is negligible.”
Downstream operations could very well become a bottleneck. Peregrine has learned through its contract manufacturing business, Avid Bioservices, that high yields — even from 1,000-L or 2,000-L bioreactors — impose operational and financial pressures on downstream processing and purification. Protein A affinity chromatography columns, for example, begin at about $1 million for resin alone and go up from there. “That’s a big investment for a small-to-midsized company,” King admits. Peregrine is handling such challenges through a hybrid approach of maintaining a revenue-generating manufacturing business that mitigates the cost of preparing for commercialization of its own products. “Not many companies have that flexibility.”
Read the Cancer Immunotherapies eBook from BioProcess International magazine.