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With Souped-Up Rituxan, Unum Plots First Foray Into T-Cell Therapy

Xconomy Boston — 

Unum Therapeutics emerged from stealth a few weeks ago with its own twist on the increasingly crowded field of cellular immunotherapy. Today the Cambridge, MA-based company is disclosing more details, not the least of which is that the technology is ready to be tested in patients.

Any cell-based immunotherapy effort is bound to attract attention these days, but Unum will be closely watched for a few scientific and strategic reasons. Unum has begun recruiting patients for the first clinical trial of what it’s calling ATTCK20. The experimental therapy is for patients with various B-cell malignancies such as chronic lymphocytic leukemia (CLL) and non Hodgkin lymphoma. ATTCK20 combines Unum’s T-cell technology with the antibody therapy rituximab (Rituxan), one of the early monoclonal antibodies to be approved and one of the most widely used in biotech history.

The trial is Unum’s first chance to prove the worth of its version of cellular immunotherapy, in which a patient’s own T cells are extracted, genetically engineered to be efficient killers of certain types of tumors, and infused back into the body. To date, most cellular immunotherapies use only the patient’s souped-up immune cells as the treatment. Adding an antibody as a therapeutic ingredient is a novel approach.

“In many ways, the trial that we’re doing right now is to provide proof of concept for what our T cells can do,” says CEO and former Novartis executive Charles Wilson.

Several companies are working on chimeric antigen receptor therapy, or CAR-T for short, which reprograms T cells to seek out and kill tumor cells that have a protein called CD19 on their surface. Paired with institutional collaborators, Novartis, Juno Therapeutics of Seattle, Santa Monica, CA-based Kite Pharma (NASDAQ: KITE), and others are testing CAR-T methods in blood cancers like acute lymphoblastic leukemia with impressive but early results so far.
But with that field increasingly crowded, some companies are eyeing next-generation approaches aimed at making the process quicker, cheaper, and safer.

One of those approaches was the center of a deal last week, when Johnson & Johnson teamed with Lexington, KY-based Transposagen Biopharmaceuticals, which is developing an “off the shelf” type of CAR-T. Pfizer is doing something similar through a deal with France’s Cellectis.

Unum CEO Charles Wilson

Unum CEO Charles Wilson

Unum is trying to be more universal. Rather than fixate on a specific cancer type or antigen—a substance that sparks an immune response, as CD19 is in the case of many of these other CAR-T approaches—Unum wants to engineer T cells with a surface protein that helps them latch onto antibodies.

The idea is to let antibodies like rituximab, which are proven to hone in on certain tumors, act as beacons. Rituximab finds tumor cells with CD20 on their surface; the Unum T cell would follow a bit later (or travel together after being infused at the same time) and bind to the rituximab, which helps form a molecular bridge to the tumor cells so the T cell can kill them.

Rituximab by itself does a pretty good job of fighting CD20-related diseases such as CLL and Non Hodgkin lymphoma. But not all patients respond to rituximab, and almost all end up taking something else after the drug stops working. Unum will first test its approach, in a variety of dose levels, in patients with chronic lymphocytic leukemia or Non Hodgkin lymphoma who either haven’t responded to rituximab or relapsed after treatment. Patients will be dosed a day or so after they get rituximab, according to Wilson.

By using this type of approach, the thinking goes, you can not only effectively supercharge a targeted antibody, but also apply a CAR-T approach to any type of cancer to which antibody therapies are being applied. Unum calls this “antibody-coupled T-cell receptor” technology, or ACTR; the name Unum, as in e pluribus unum (“out of many, one”) reflects that universal approach.

ACTR was developed by Dario Campana, who created the platform at the National University of Singapore and St. Jude Children’s Research Hospital. Campana also developed a CAR-T approach that’s … Next Page »

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