A clinical investigator at Children’s Hospital of Los Angeles, Hisham Abdel-Azim, MD, MS, and colleagues, have completed a study where they engineered T-cells to identify and target multiple sites on acute lymphoblastic leukemia cells rather than just one. This breakthrough could lead to clinical trials to test the therapy.
Acute Lymphoblastic Leukemia (ALL)
Being the most common childhood cancer, most children actually respond to chemotherapy; however, some experience resistant or relapsed disease. CAR-T therapy was developed to bridge the gap for those children for whom chemotherapy wasn’t enough or just didn’t work.
CAR-T Therapy & Limitations with Missing CD-19
This approach uses the patient’s own T-cells, isolating and genetically modifying them to recognize CD-19—a protein (antigen) found on leukemia cells. When the T-cells are introduced back into the patient, the immune system attacks the cancer. Although CAR-T offers meaningful results for many, nearly half of patients who received the therapy later relapsed because the cancer stopped producing the protein CD-19 and became invisible to the T-cells.
‘A Trident instead of a Spear’
Dr. Abdel-Azim and team, including Nabil Ahmed, MD, MPH of Baylor College of Medicine and Texas Children’s Hospital, colaborated to engineer a T-cell that targets not only CD19, but also two other proteins found on leukemia cells—CD20 and CD22. Dr. Ahmed compared it to “using a trident to attack cancer instead of a spear” noting the team used this “three-pronged weapon against leukemia cells in pre-clinical studies and developed new methods to monitor how well it worked”.
The new TriCAR-T cell can target CD-19, CD-20, and CD-22, significantly improving the effectiveness of targeting CD-19 alone, based on the study findings. As the leukemia cells stop producing CD-19, and hence making themselves invisible to the FDA-approved CAR-T cells, the TriCAR-T cell were still effective in attacking the cancer. Moreover, as Dr. Abdel-Azim notes, “These new CAR-T cells bind to more cancer cells and these connections are much stronger.” He continued, “Not only do they bind better, but they are binding again and again.” These connections evidence the leukemia cell killing power of the new CAR-T cells. The goal here: more T-cell binding means a stronger fight against the cancer.
Innovation not Possible without Collaboration
The researchers will need to prove, via randomized controlled trials, the effectivity and safety of the TriCAR T cell therapy prior to actual use in the clinic; but the early lab results are promising. Dr Abdel-Azim concluded, “Just like attacking more than one antigen is more effective in the fight against leukemia, so too is combining investigative forces. Scientific findings like these would not be possible without collaboration.”
William Lawrence and Blanche Hughes Foundation, Kure It Cancer Research Foundation, and a Stand Up to Cancer-St. Baldrick’s Pediatric Cancer Dream Team Translational Research Grant.
Los Angeles Children’s Hospital
Founded in 1901, Children’s Hospital Los Angeles is ranked the top children’s hospital in California, and fifth in the nation for clinical excellence with its selection to the prestigious U.S. News & World Report Honor Roll of children’s hospitals. Clinical care is led by physicians who are faculty members of the Keck School of Medicine of USC through an affiliation dating from 1932. The hospital also leads the largest pediatric residency training program at a freestanding children’s hospital of its kind in the western United States. The Saban Research Institute of Children’s Hospital Los Angeles encompasses basic, translational, and clinical research conducted at CHLA.
Hisham Abdel-Azim, MD, MS, investigator, The Saban Research Institute of Children’s Hospital Los Angeles; Associate Professor of Pediatrics at the Keck School of Medicine of USC.