Academic team assembles a 'homegrown' immunotoxin for blood cancers

An oncologist at the University of Minnesota has devised a "homegrown" bispecific antibody that binds to both CD19 and CD22, proteins found on the surface of B-cell blood cancers, and drops a toxic payload on the targeted cells. In a Phase I trial with 10 evaluable patients with treatment resistant pre-B acute lymphoblastic leukemia, chronic lymphocytic leukemia, or non-Hodgkin lymphoma, two had a durable response, with one complete remission. And that is setting the stage for a mid-stage study of a drug that has been pushed this far largely with private donations.

The drug combines antibody fragments that zero in on both the CD19 and CD22 proteins, both high-value targets in the world of blood cancer research. The team then fused on a bacterial diphtheria toxin that enters the cancer cell once the fragments bind to it, killing it with a toxic dose.

In the Phase I, the team working with Daniel Vallera says they had not reached the maximum dose that could be used safely. And going into Phase II, the investigators are looking to amp up the doseage, looking for a higher response rate among patients who had failed multiple therapies.

"In this Phase I trial, we found a safe dose of the drug that has biological activity," says Vallera. "Of the 10 evaluable patients, two of them responded. We are planning a Phase II trial with this drug. It will focus on giving more cycles of treatment, which we believe will dramatically enhance the response rates. We were surprised that the drug was effective enough to entirely eliminate the cancer in one of our patients. Further, we expected the patients to make antibodies against the bacterial toxin and thus reject our drug. Surprisingly, this did not occur in the majority of our patients [70 percent]. We need to study more patients to understand why they did not produce neutralizing antibodies. However, we also have been working to create a less immunogenic form of the toxin for the next-generation drug."

Vallera added, "Another important fact about our drug is that it was home-grown, meaning there was no commercial partner, which is rare. The drug was funded mostly with private donations including individuals that have lost loved ones to cancer."

- here's the release

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