Alex's Lemonade Stand Foundation for Childhood Cancer

Background

T-cells have proved safe and effective for the treatment of certain types of cancer. However, T-cell efficacy against most solid tumors is limited by the immunosuppressive microenvironment generated by tumor cells and their infiltrating stroma. Myeloid-derived cells are potent controllers of the tumor microenvironment and can alter the fate of tumor-specific T-cells.

Background

Langerhans cell histiocytosis (LCH) is a rare form of cancer that occurs mostly in children. The incidence of LCH is 3 to 5 cases per million children, similar to that observed in Hodgkin Lymphoma or acute myeloid leukemia. Despite similar incidence and survival, LCH patients have benefited from far less research funding and attention than other childhood hematologic neoplasias, likely due to incomplete understanding of the disease. LCH is caused by abnormal proliferation of cells derived from bone marrow.

Background
Immunotherapy with genetically modified T cells has the potential to improve outcomes for children with cancer. We have recently developed a new class of antigen-specific T cells, Engager T cells, that not only recognize tumor cells, but also redirect bystander T cells to tumors. This was achieved by genetically modifying T cells to secrete bispecific T-cell engagers. However, cancer patients also have a large reservoir of NK cells that could be harnessed to destroy malignant cells.

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.