Despite the progress of therapies that coax the immune system to fight cancer, these treatments don’t work for all patients. When they are effective, some patients experience serious side effects. TScan Therapeutics CEO David Southwell says his company aims to improve cancer immunotherapy on both fronts.
TScan’s research is still in the lab, but the company is mapping a course that could lead to human testing in two years. To get there, the Cambridge, MA, startup has raised $48 million to fund its research and development of a type of cancer treatment called T-cell receptor therapy. The company announced the financing Wednesday.
A T cell, the frontline defender of the immune system, has receptors on its surface that bind to an antigen to prompt an immune response. T-cell receptor (TCR) therapy involves taking a patient’s T cells and modifying them in a lab so that they can better recognize and target the antigen that will trigger an immune response to cancer. These modified cells are multiplied in a lab and then infused into the patient.
The approach is similar to CAR-T therapies, which have reached the market in products from Novartis (NYSE: NVS) and Gilead Sciences (NASDAQ: GILD). But CAR-T therapies, which target a protein on the surface of a cancer cell, have only been approved for blood cancers. Southwell says TCR therapies could work for solid tumors, but the challenge is identifying TCRs that could be used in cancer immunotherapy.
TScan’s technology, which is based on the research of Stephen Elledge, a professor of genetics and medicine at Harvard Medical School and Brigham and Women’s Hospital, was developed to screen tumor cells for undiscovered TCRs. Southwell says the technology can quickly screen a large number of samples and identify which TCRs interact with particular antigens. To identify potential side effects, TScan also screens the complete set of proteins encoded by the human genome to assess the biological interactions between T-cells and their targets.
“That’s so crucial for TCR [therapies] because they’re so potent,” Southwell says.
That potency can be deadly. While TCR therapies can hit tumors, they can also affect normal cells. UK-based TCR therapy developer Adaptimmune (NASDAQ: ADAP) stopped work on one of its early drugs after heart complications linked to the drug led to patient deaths in a melanoma study. That Adaptimmune therapy was developed to hit a cancer-specific protein, but scientists later found it also recognized and targeted a protein found in heart tissue, which led to the complications, according to a 2015 report published about the study.
Southwell says TScan’s approach could be used to develop cancer treatments from a patient’s own T-cells, which is the way that CAR-T therapies are made. But he adds that the company is also building a cache of TCRs that could potentially treat many patients. A TCR from this collection would first need to be tested to ensure immunological compatibility, but Southwell says using such a repository could be much faster than trying to develop personalized TCR therapies for every patient.
The TScan technology could potentially address autoimmune disorders and infectious diseases but cancer is the company’s focus for now, Southwell says. Besides Adaptimmune, other companies that have a head start in TCR therapy R&D include TCR² Therapeutics (NASDAQ: TCRR) and Adaptive Biotechnologies (NASDAQ: ADPT). Before Adaptive revealed its ambitions to become a TCR drug developer, the company built a business sequencing DNA of immune cells for clinicians and drug companies. At its start, the Seattle company was known as Adaptive TCR—for T-cell receptor.
Southwell says TScan could identify lead compounds in the next six to nine months, then move them into preclinical research. He expects the new cash will last until 2021, when the company will be in the clinic or close to it. Exactly how long the cash lasts could be affected by other factors, including the outcome of ongoing partnership discussions with pharmaceutical companies, he says.
TScan first raised money a year ago in a small Series A round that Southwell described as seed financing. The $48 million in capital announced Wednesday is a combination of its Series A and B rounds, he said. New investor Novartis Institutes for Biomedical Research joined earlier investors Bessemer Venture Partners, GV, Longwood Fund, and Novartis Venture Fund in the Series B financing.