Precursor-B acute lymphoblastic leukemia (ALL) is the most common cancer in childhood.
Despite major advances in ALL therapy, 20% of children and 40-50% of adults fail state-of-the
art first-line treatment. But there is a strong need for alternative treatments to cure
chemotherapy-refractory and relapsed B cell malignancies in pediatric patients. Relapsed and
refractory B cell malignancies remain a therapeutic challenge, as these diseases are
characterized by adverse survival. These cancers share a cell origin from the B-cell lineage
and consequent surface expression of B-lineage markers such as CD19 and CD22. Chimeric
antigen receptor (CAR) engineered T cell therapy has recently emerged as a new modality to
target B cell malignancies. CARs couple a single-chain Fv (scFv) domain directed against a
B-lineage-specific antigen to T-cell activating intracellular signaling domains. CAR
gene-modified T cell interaction with target cells occurs in a HLA-independent fashion, so
that a single vector can be used to treat all patients with cancers that express the target
antigen. Miltenyi Biotec has established a semi-automated manufacturing process that can be
made available to academic settings for systematic exploration of CAR strategies in advanced
clinical studies. Closed-system operation, improved robustness, simplified work flows, and
reduced labor intensity, while maintaining strict adherence to regulatory guidelines, allows
for decentralized manufacturing. In the proposed phase II study, the investigator will
explore autologous 2nd generation CD19 CAR T cell products in patients with relapsed and
refractory disease incurable with standard therapies.