Optimizing Engager T-cells for CD19+ Malignancies
Background
Using the patient's own immune system to fight cancers is a promising approach to improve outcomes for pediatric cancer patients who do not benefit from current therapies. However, the body's immune defenses against cancers often fail because the cancers do not induce or actively inhibit immunity. Cancer treatments consisting of the infusion of T cells (one component of the patient's own immune system) that recognize CD19, a molecule present on many blood cancers, have shown promise in early clinical studies.
Project Goal
We have developed a new strategy to produce CD19-specific T cells with a genetic approach that redirects not only the genetically modified cells, but also unmodified T cells to CD19-positive blood cancer cells. Preliminary studies have shown good activity against leukemia in preclinical models that closely mimic human disease. We now plan to build on our encouraging results, and will evaluate if additional genetic modifications of CD19-specific T cells and/or targeting additional molecules present on many blood cancers enhances anti-tumor activity. If our pre-clinical approach is successful and a clinical study is justified, we have the resources to develop such a study at our center.
"Receiving funding from Alex’s Lemonade Stand will help us find innovative techniques for treatment of childhood leukemia using the patient’s own immune system." ~Mireya Velasquez, MD
Project Update
We are harnessing the patient's own immune system to target leukemia and lymphoma cells that have CD19 antigen, a protein, on their cell surface. We continue to work on improving these CD19-specific T cells (CD19 Engager T cells) to have better anticancer activity. Supported by the Alex's Lemonade Stand Young Investigator Award, we have modified these CD19 specific T cells so that they express proteins named CD80 and 41BBL on their surface. These proteins can bind with their counterparts on other T cells and help with 'activating' them. We have seen that making these changes is a way to have a more consistent antitumor activity at lower doses than when using CD19 Engager T cells only. We are also working on ways to help prevent leukemia/lymphoma from developing resistance by aiming our T cells at both CD19 and CD22 antigen.
