Headshot of David Apelian

BlueSphere Bio Aims for Next-Level Personalized Cancer Cell Therapy

Chimeric Antigen Receptor T cell (CAR-T) therapies, such as those developed by Kite Pharma, have revolutionized the approach to treating hematological cancers, but the therapies have limitations due to toxicity concerns. Pennsylvania-based BlueSphere Bio believes its approach through the use of TCR-T cell therapies will provide a more precise treatment option for patients.

CAR-T cells are engineered in a laboratory to recognize a specific antigen on a cell and then re-administered into a cancer patient. The CAR-T cells should, if all goes as planned, multiply within the body and target the antigen and eliminate the threat. However, CAR-T cells are not naturally occurring and while they have shown promise, they also have limitations, particularly in solid tumors.  BlueSphere’s TCR-T cell therapy uses the body’s own T cells and activates them to attack different forms of cancer.

It’s that more natural approach to targeting cancer that BlueSphere Chief Executive Officer Dr. David Apelian believes will lead to a broader and safer approach. Apelian touted the pioneers who first developed CAR-T therapies, such as the University of Pennsylvania’s Dr. Carl June. Apelian said the approach is a breakthrough in the way the immune system can treat cancer. However, due to the toxicity concerns surrounding current CAR-T therapies, Apelian said BlueSphere is advancing the development of TCR-T cells in the same manner in which the body uses them to fight infections and diseases. And that natural approach is where Apelian believes the difference will be seen with BlueSphere’s cell therapies.

TCRs are specific receptors unique to T cells that can target intracellular antigens. By harnessing the specificity of these TCRs, BlueSphere is able to genetically engineer TCR-T cells to recognize target antigens, such as those that are cancer-specific. Through this approach, Apelian believes they will be closer to the end goal for companies that were attempting to develop vaccines for cancer, such as GlobeImmune, where he spent eight years as Chief Medical Officer.

“If you can identify receptors that will direct the T cells to kill the tumor, then amplify them in a greater number and reintroduce them into the patient, you’ll be able to leapfrog the whole vaccine process for cancer,” Apelian said.

Through the use of its TCXpress™ technology platform, the company can take immune cells from the tumor, screen and capture thousands of T cells, and figure out which ones want to kill the cancer. The technology, which was developed in the laboratory of Dr. Mark Shlomchik, was licensed from the University of Pittsburgh and is a proprietary high-throughput and efficient TCR search and capture platform.

Using TCXpress™, BlueSphere’s goal is to find multiple T cell receptors to turn the tide against the cancer, Apelian said. The reason for multiple receptors is due to the various mutations that can occur within a tumor. The goal is to pick multiple unique hits that should be able to impact the tumor and its different mutations, he said. Once those hits have been determined, selected TCRs are engineered into the patient’s healthy T cells, and the T cells are reintroduced in large numbers. Before a patient is treated, Apelian added that BlueSphere will conduct in vitro work to determine which T cell receptors will best work.

“Our TCR search and capture platform, TCXpress™, is the beating heart of the company. It will always be an integral part of our approach,” Apelian said.

So far, CAR-T therapies have only been approved for use as a treatment for blood cancers. Although there have been multiple attempts to use this approach in solid tumors, none have succeeded so far. This is due, in part, because CAR-T therapy can only target surface proteins in contrast to the short peptides targetable by TCRs.  However, Apelian predicts that the use of natural T cells will allow the approach to work in both solid and liquid tumors.

“A T cell receptor can recognize the tiny bit of foreign protein presented by cells. There’s a whole universe that T cells receptors can see and attack,” Apelian said. He added that because of their approach, BlueSphere believes they will have a meaningful impact against cancer.

But, it will take some time before the company can test its hypothesis. Apelian anticipates BlueSphere will enter the clinic in late 2022. The company’s first target will likely be in bone marrow recipients with high-risk leukemia.

BlueSphere is a spinout of UPMC Enterprises, the venture capital arm of the UPMC led by Jeanne Cunicelli, and has enough financial runway to cover its ongoing research and planned clinical programs through 2024. Earlier this year, the startup raised $105 million in a tranched Series B investment from UMPC Enterprises, which also provided seed funding for gene therapy Code Bio earlier this year. That came on the heels of $15 million in a Series A.

Apelian said TCXpress™ will provide BlueSphere the ability to partner with other cell therapy companies taking aim at different kinds of cancer. He also believes there is potential for this approach in autoimmune diseases.

Even as BlueSphere advances its TCR-T cell therapy approach toward the clinic, Apelian also pointed to the company’s solid tumor virtual patient program, which will allow the company to guide the next R&D steps for its pipeline. The virtual patient program harnesses the capabilities of TCXpress™ as well as its proprietary patient-specific neoantigen discovery platform, NEOXpress™. This will allow BlueSphere to build a repository of tumor data for each patient that Apelian likened to a baseball box score. The information will provide a profile of the neoantigen, the T cells found in the tumor, the number of hits, and the potential to destroy the tumor. Noting the cutting edge capabilities of the virtual program, Apelian said this is “as close to a clinical study as you can get,” prior to initiating the clinical study itself.

“We have some really exciting stuff going on right now that could change the way we approach cancer treatment. This is next-generation precision medicine,” Apelian said.