title: CAR T-Cell Therapy: The Role of Physical Barriers and Immunosuppression in Lymphoma.
abstract: Chimeric antigen receptor (CAR) T-cells have shown remarkable results in patients with B-cell leukemia and lymphoma. However, while CAR T-cells have shown complete responses in a majority of patients with acute lymphoblastic leukemia (ALL), lymphomas are more difficult to treat. Different CAR designs and conditioning protocols seem to affect the persistence of patient responses. However, factors that determine if patients receiving the same CARs will respond or not remain obscure. In Sweden, a phase I/IIa trial using third-generation CAR T-cells is ongoing in which we intend to compare tumor biology and immunology, in each patient, to treatment response. CAR T-cell therapy is a powerful tool to add to the treatment options for this patient group but we need to perform the necessary basic research on the multifactorial mechanisms of action to give patients the best possible option of survival. Such studies are also crucial to expand the success of CAR T-cells beyond CD19+ B-cell malignancy. This review will focus on possible barriers of treating lymphoma to define factors that need to be investigated to develop the next generation of CAR T-cell therapy.
authors.affiliation: Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University , Uppsala, Sweden .
authors.forename: Gunilla
authors.initials: G
authors.lastname: Enblad
authors.affiliation: Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University , Uppsala, Sweden .
authors.forename: Hannah
authors.initials: H
authors.lastname: Karlsson
authors.affiliation: Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University , Uppsala, Sweden .
authors.forename: Angelica S I
authors.initials: AS
authors.lastname: Loskog
mesh_terms: D000818:Animals; D006801:Humans; D007165:Immunosuppression Therapy; D007167:Immunotherapy; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D008223:Lymphoma / Q000276:immunology / Q000628:therapy*; D050506:Mutant Chimeric Proteins / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000637:transplantation*; D059016:Tumor Microenvironment
chemical_list: D050506:Mutant Chimeric Proteins; D011948:Receptors, Antigen, T-Cell