Several groups have introduced novel receptors into T cells to redirect these cells to specific tumor targets such as CD19 for CLL, CD20 for B cell non-Hodgkin lymphoma and CD19 for ALL .
These adoptively transferred T cells have not persisted for very long and a number of groups are exploring strategies to improve persistence of the cells. One approach has been to utilize sub-populations of T cells for modification, such as central memory T cells (chimeric antigen receptor T cells, CAR-T cells).
As an example, two intriguing reports described three patients with relapsed or refractory CLL who received autologous T cells modified with a lentiviral vector expressing chimeric antigen receptor with specificity for CD19, coupled with CD137 and CD3-zeta signalling domains after a preparatory regimen. All three patients demonstrated a tumor response, which persisted in one for at least 10 months. Toxicity included severe tumor lysis syndrome.
Ongoing studies are investigating the use of chimeric antigen receptor T cells (CAR-T cells) directed at CD19. As an example, an intriguing report described five patients with relapsed B cell acute lymphoblastic leukemia (ALL) who received autologous T cells modified with a lentiviral vector expressing chimeric antigen receptor with specificity for CD19, coupled with CD137 and CD3-zeta signalling domains after a preparatory regimen.
All five patients demonstrated a molecular remission, which allowed them to become eligible for subsequent hematopoietic cell transplantation. Toxicity included significant cytokine elevations, some of which required treatment with steroid therapy. A similar approach has been used for patients with other hematologic malignancies, including chronic lymphocytic leukemia and non-Hodgkin lymphoma. Further follow-up of these patients and larger trials are needed to determine the efficacy of this approach.