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LLS-funded researchers from University of Pennsylvania and Children’s Hospital of Philadelphia continued to present more promising data three and a half years after beginning a clinical trial demonstrating the first successful and sustained use of genetically engineered T cells to fight leukemia. The team presented their latest findings today at the American Society of Hematology’s annual meeting in New Orleans.


 

The latest results of studies involving both adults and children with advanced blood cancers for whom all previous therapies had failed, showed that 89 percent of the acute lymphocytic leukemia (ALL) patients had a complete response rate.


 

LLS has invested $15 million in this team’s work, with an additional $6 million committed through 2017.


“In a very short time, we’ve learned so much about how CTL019 works and how powerful it can be,” said the research team’s leader, Carl H. June, M.D., Richard W. Vague Professor in Immunotherapy in the department of Pathology and Laboratory Medicine and director of Translational Research in Penn’s Abramson Cancer Center, in a UPENN news release. “Our findings show that the human immune system and these modified ‘hunter’ cells are working together to attack tumors in an entirely new way.”


 

The research team, which includes investigators who treat patients at both the Hospital of the University of Pennsylvania and the Children’s Hospital of Philadelphia, announced findings from trials of three different groups of patients:


 

15 of 32 adult patients with chronic lymphocytic leukemia (CLL) (47 percent) responded to the therapy, with seven of those experiencing a complete remission of their disease. Results of both the completed pilot study of 14 CLL patients and results thus far of the first 18 patients in a Phase II, dose-optimization trial were  presented.


 

• 19 of 22 pediatric patients with ALL (86 percent) experienced complete remissions. The first pediatric patient treated with the protocol, who is now 8 years old, remains in remission 20 months later. Five patients have relapsed, including one whose tests revealed new tumor cells that do not express the protein targeted by the reprogrammed cells.


 

• All five of the first adult ALL patients treated thus far experienced complete remissions, the longest of which continues six months after treatment. One patient subsequently underwent a bone marrow transplant and remains in remission. One patient relapsed after three months with disease that also tested negative for the engineered cell target.


 

The newly built T cells target tumor cells using an antibody-like protein, called a chimeric antigen receptor (CAR), which is expressed on the surface of the T cells and designed to bind to a protein called CD19, which is found on the surface of the cancerous B cells associated with both CLL and ALL. The modified cells are then infused back into the patient's body.


 

“These findings show real promise for critically ill patients who have run out of options,” said Lee Greenberger, Ph.D., LLS chief scientific officer. “Time will tell how enduring these remissions prove to be.”

 

One of the researchers from the team, Stephan A. Grupp, M.D., Ph.D., of Children's Hospital of Philadelphia, said that very early in his career his very first grant was from LLS and enabled him to continue to pursue research in the field of blood cancer.

 

(Source material: UPENN)

 

(Photo below: l-r, Michael Kalos, Ph.D., formerly of UPENN, now chief scientific officer, cancer immunobiology at Eli Lilly and Company, and Stephan A. Grupp, M.D., Ph.D., Children's Hospital of Philadelphia.)

 

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