Integration of a CD19 CAR into the TCR Alpha Chain Locus Streamlines Production of Allogeneic Gene-Edited CAR T Cells.

Adoptive cellular therapy using chimeric antigen receptor (CAR) T cell therapies have produced significant objective responses in patients with CD19 hematological malignancies, including durable complete responses. Although the majority of clinical trials to date have used autologous patient cells as the starting material to generate CAR T cells, this strategy poses significant manufacturing challenges and, for some patients, may not be feasible because of their advanced disease state or difficulty with manufacturing suitable numbers of CAR T cells. Alternatively, T cells from a healthy donor can be used to produce an allogeneic CAR T therapy, provided the cells are rendered incapable of eliciting graft versus host disease (GvHD).

Know your neighbors: Different tumor microenvironments have implications in immunotherapeutic targeting strategies across MB subgroups.

Medulloblastoma (MB) is the most common pediatric brain tumor with few reports of successful immunologic targeting. We have recently demonstrated the immune tumor microenvironment as well as response to immune checkpoint blockade differ across subtypes of murine MB.

Differential Immune Microenvironments and Response to Immune Checkpoint Blockade among Molecular Subtypes of Murine Medulloblastoma.

Purpose: Despite significant strides in the identification and characterization of potential therapeutic targets for medulloblastoma, the role of the immune system and its interplay with the tumor microenvironment within these tumors are poorly understood. To address this, we adapted two syngeneic animal models of human Sonic Hedgehog (SHH)-driven and group 3 medulloblastoma for preclinical evaluation in immunocompetent C57BL/6 mice.

Experimental Design And Results: Multicolor flow cytometric analyses were used to phenotype and characterize immune infiltrating cells within established cerebellar tumors.

Chasing cancer with chimeric antigen receptor therapy.

Many attempts to use genetically modified T cells to halt tumor progression have been met with disappointment and significant challenges in the successful application within human patients. Porter et al., however, describe the use of genetically modified lymphocytes bearing a chimeric antigen receptor that bypasses many of the common limitations of adoptive lymphocyte therapy.