The President of the United States declared a war on cancer fifty years ago. At the time, the idea of one’s own immune system killing the cancer was far from mainstream. Technological innovation and drug discovery has progressed by leaps and bounds since then. Our collective understanding of the critical role the immune system plays in fighting cancer is transforming the management of this still devastating disease.
Immunotherapies are now considered standard of care in many tumor types. The powerful convergence of biology and technology has fueled the generation of rich, multi-dimensional, high resolution genomics and proteomics data to better understand cancer biology and the immune system. We now have deeper insights into disease factors that have helped inform the discovery and development of new transformative cancer therapies — these span antigen directed T-cell therapies, bispecific antibodies, gene therapies, and personalized vaccines.
Harlan Robins, co-founder and chief scientific officer of Seattle-based Adaptive Biotechnologies, says the most powerful tool to keep people healthy is the immune system. Our body works around the clock to identify and treat diseases, often before we even experience symptoms. This is the core principle of immune medicine and the power of harnessing the adaptive immune system to transform the way most diseases are diagnosed and treated. This forms the basis of Adaptive’s immune medicine platform.
Translating the power of the immune system
With partner Microsoft, Adaptive is combining its immune medicine platform and artificial intelligence (AI) plus machine learning to decode the human adaptive immune system. The goal is to build a massive map of the immune response to thousands of different diseases. Together with Microsoft, Adaptive is translating biology into data and then turning this data into actionable information to transform the diagnosis and treatment of disease. The goal of this map is to be able detect and diagnose many different diseases simultaneously — all from a simple blood sample.
Because the immune system both detects and treats disease, this very same map can also be used to discover novel therapeutic targets in many different diseases for the development of transformative medicines.
A treatment paradigm shift in cancer
In 2019, Adaptive partnered with Genentech to discover and develop novel, neoantigen directed T-cell therapies for the treatment of a broad range of cancers. The companies are combining Genentech’s cancer immunotherapy and clinical development expertise with Adaptive’s immune medicine platform to develop and commercialize a new model of shared and truly personalized cancer cellular therapies.
How does it work? While there are many different approaches to cell therapy, the general concept is the same: a specific subset of a person’s immune cells, called T-cells, are extracted, modified, multiplied and reintroduced into the body to attack and destroy tumor cells. For neoantigen-directed T-cell therapies, this means genetically engineering a person’s own T-cells with specific T-cell receptors (TCRs) that recognize that person’s own tumor-specific neoantigens. The big challenge, though, is choosing the right neoantigens and the right TCR to target in either an ‘off the shelf’ product or a truly personalized therapy. Each person’s T-cells carry an incredibly diverse and unique collection of TCRs. This diversity allows the immune system to specifically recognize foreign proteins, including cancer neoantigens.
“We believe that targeting neoantigens could be the most effective approach to harness a person’s immune system to fight cancer,” said Ira Mellman, vice president of cancer immunology at Genentech, who is working closely with Adaptive on the partnership. “By identifying the right neoantigens and the best T-cell receptors against those neoantigens, we have the potential to create highly targeted cancer therapies that transform how cancer is treated.”
Genentech recognized the power of the Adaptive platform to identify at scale naturally occurring, fully human T-cell receptors that are potent and do not need further engineering to recognize a cancer target. Adaptive also comprehensively evaluates TCRs to confirm specific binding to cancer antigens found in a patient’s tumor. By sifting through millions of TCRs, Adaptive is able to select the best potential therapeutic candidates with highest likelihood to be effective and safe in fighting a patient’s cancer. “We find T-cell receptors that bind to cancer-related antigens. We funnel them down to the ones that show strong target binding, cancer cell killing and have minimal off-target effects, selecting the best ones with the potential to become next-generation cellular therapies for patients with cancer,” said Sharon Benzeno, chief business development officer and head of drug discovery at Adaptive.
Adaptive is combining its TCR discovery approach with AI and machine learning to one day be able to accurately predict TCR to cancer antigen binding and more rapidly identify therapeutic grade TCRs. This has the potential to significantly shorten turnaround time for the treatment of patients with their own personalized cellular therapy. The pairing of advanced sequencing technologies, machine learning, and artificial intelligence are helping to accelerate innovation and to drive the next wave of drug discoveries and the development of transformative medicines.
When Robins began his career, the idea of harnessing the immune system to kill cancer was a pipedream. “Now, our understanding of the immune system has completely transformed the way we treat cancer and so many similarly life-threatening diseases,” he said. “At Adaptive, we’re excited about the potential of using this knowledge to save lives.”
To learn more, visit www.adaptivebiotech.com/cellular-therapy.