Adaptimmune's CMO Moves Forward With SPEAR T Cell Therapies

U.K.-based Adaptimmune Ltd. started the New Year with news it successfully manufactured the first SPEAR-T cells for use in a multiple tumor study as it continues to transition its NY-ESO SPEAR T-cell therapy program to its partner GlaxoSmithKline.

Adaptimmune rolled into the J.P. Morgan Healthcare conference armed with initial safety data from its two ongoing pilot studies of SPEAR T-cells targeting MAGE-A10. The studies are in non-small cell lung cancer (NSCLC) and a triple tumor study in bladder, melanoma and head and neck cancers. Although the studies are small, only eight patients in each, no toxicity issues have been seen, the company said.

Adaptimmune is making strides on becoming a fully integrated cell therapy company behind its T Cell Receptor technology, Adaptimmune Chief Medical Officer Rafael Amado told BioSpace in an exclusive interview.

While CAR-T therapies have been shown to be effective in treating blood cancers so far, they have not been as effective in solid tumors. Amado said that is due to a myriad of reasons, including the location of target proteins being on the surface of hematological tumors, while solid tumors are much tougher with the proteins inside the tumor. He also pointed to the larger antigen load in hematological targets. In solid tumors, the antigen load is lower, which makes it difficult for the T cells to stimulate, Amado said.

"There’s a constellation of parameters that make it harder. The macro environment of the cancer cell engineers ways to resist the strategy," Amado said. "With TCRS, they’re not limited by the idea of surface proteins, which allows us to choose a large variety of targets. We have the ability to identify the target and that can play in a variety of spaces."

Amado said efficacy and safety data from the Phase I trial will continue to accumulate throughout the year and the company plans to share it at various scientific conferences.

Adaptimmune is using SPEAR T-cells in two clinical trials targeting MAGE-A10, one in NSCLC, and a triple tumor study in bladder, melanoma, and head and neck cancers. Both studies are dose escalation trials that evaluate three doses of transduced SPEAR T-cells, administered after a lymphodepleting chemotherapy regimen.

In addition to the MAGE-A10 trial, Adaptimmune is also targeting MAGE-A4. The newly manufactured SPEAR T-cell at the Philadelphia site will be used in a multiple tumor study in bladder, melanoma, head and neck, ovarian, non-small cell lung, esophageal, and gastric cancers.

The announced manufacture of the SPEAR-T cell is a key milestone for the company. Amado told BioSpace it important to the company to control its own manufacturing process. That will give the company freedom to schedule patients, optimize and escalate as programs progress, he said.

"We’ll be treating patients with drugs they manufacture, which will be a huge step in the process. It’s been a lot of work and is now paying off. We’re also controlling our own supply chains. We’ll control the entire process from vein to vein," Amado said.

By manufacturing its own SPEAR T-cells, the company will be able to deliver cells for up to 300 patients per year. A possible expansion would enable the company to manufacture the therapies for up to 1,000 patients per year. Amado said the manufacturing space will likely be where potential growth originates. The company has not yet released any plans yet for that possible manufacturing expansion.  

Over the next few months, Amado said the company will have several goals that include completing the transaction of the NY-ESO SPEAR T-cell therapy program with GSK. The two companies initiated their collaboration in 2014 and last year the pharma giant exercised its option to exclusively license Adaptimmune’s NY-ESO SPEAR T-cell therapy program. Additionally, the company will concentrate on its three internal trials with a focus on dose escalation across tumor types.