Hopeful Research for MM patients -- Toxin-Based Therapy Dramatically Increases Survival in Mice with Human Tumor Cells


New type of targeted therapy shows promise in preclinical models of B-cell malignancy

An investigational, bacterial toxin-based therapy targeted to the protein CD38, which is found on the surface of many human blood cancer cells, including multiple myeloma cells, dramatically increased survival in mice bearing human tumor cells, according to data presented at the American Association for Cancer Research special conference, Hematologic Malignancies: Translating Discoveries to Novel Therapies, held Sept. 20-23.

"Although there are treatment options for patients with multiple myeloma, there is currently no cure, and many patients receive multiple treatments to manage the disease," said Erin K. Willert, PhD, executive vice president of research and development at Molecular Templates Inc. in Georgetown, Texas. "In this study, we found that the growth of human cancer cells in mice was substantially decreased, or the cells were even eliminated, following treatment with our investigational CD38-targeted therapy.

"Our results give us confidence in moving the drug forward toward clinical trials for CD38-positive B-cell malignancies such as multiple myeloma," continued Willert. "Moreover, since our CD38-targeted engineered toxin body works differently than current therapeutics, we think that our investigational therapy has the opportunity to be effective in cases of relapsed or refractory multiple myeloma and other CD38-positive B-cell malignancies."

The investigational therapy studied by Willert and colleagues is a CD38-targeted engineered toxin body. According to Willert, engineered toxin bodies recognize a specific protein on the surface of a cancer cell, CD38 in the case of this investigational therapy, and deliver a modified bacterial toxin that enters the cancer cell and then shuts down protein production and kills the cell.

In mice bearing human cancer cells, the lowest dose of the investigational CD38-targeted engineered toxin body (0.05 mg/kg body weight) significantly reduced tumor burden: Mean tumor burden was 29 percent of the burden in control mice. Treatment with higher doses, 0.5 and 2 mg/kg, resulted in mean tumor burden of less than 1 percent of control.

The investigational CD38-targeted engineered toxin body increased median survival. Control mice had a median survival of 34 days compared with 59.5 days for mice treated with the lowest dose of the investigational therapy. Among mice who received 0.5 or 2 mg/kg of the investigational therapy, 90 percent and 100 percent were alive at day 60 of the study, respectively.

"Based on comparisons with another engineered toxin body therapy that is entering clinical testing, we believe the concentrations of the investigational CD38-targeted engineered toxin body we used in the mice in this study will be relevant to the doses used in humans," said Willert. "However, more preclinical studies are needed before we can test the therapy in the clinic."

Makes me wish I was a mouse!

I know what you mean, Victor. There are a lot of heroic little martyr mice that have helped rare disease patients. Three cheers for the mice! And may we get some breakthrough human trials soon.

More encouraging news, your the best


Rodney, my friend, how have you been. I sm still here, doing ok, just started my 6th cycle of carfilzomid and Rev post transplant maintenance. Still no CR, but still slowly dropping, just glad to be here. And you?

My its great to here from you, I am still here also, just finished my first 2 doses of kryprolis. No results yet but hoping it works. I have become double refractory to velcade and revlimid. Wouldn't be grand for them to come up with a cure. Please get better so we can visit one day, and stay away from Dallas. I needed a transfusion last week, they scare me as I feel very dependent on someone else for keeping me going, although it does feel good sorta reminds me of how it was before mm.

Enjoy life my friend