CAR T Cell Therapy in Acute Lymphoblastic Leukemia and Potential for Chronic Lymphocytic Leukemia.
Adoptive transfer of autologous T cells engineered to express a chimeric antigen receptor (CAR) represents a powerful targeted immunotherapy that has shown great promise in some of the most refractory leukemias. CAR-modified T cells directed against CD19 have led the way, setting a high standard with remission rates as high as 90 % in clinical trials for relapsed/refractory acute lymphoblastic leukemia (ALL). Yet, the first demonstration of efficacy was in another disease, chronic lymphocytic leukemia (CLL), in which CD19-targeted CAR T cells eradicated bulky, highly refractory disease. Despite early encouraging results, clinical trials in CLL have yielded lower response rates, revealing disease-specific differences in response in this form of immunotherapy. Ongoing research focused on identifying and overcoming these limitations, promises to improve response rates. Beyond the induction of remission, the transformative impact of engineered T cell therapy lies in its potential for long-term disease control. With longer follow-up and durable T cell persistence now reported, we are closer to answering the question of whether sustained remissions are possible with CAR T cell monotherapy. As might be expected with a highly effective therapy using a single mechanism of action, escape pathways have emerged. Combinatorial approaches are needed to anticipate and prevent this mode of relapse. Lastly, toxicity management is vital to ensure the safety of this exciting cancer immunotherapy.
Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Nathan
N
Singh
Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Noelle V
NV
Frey
Division of Oncology, The Children's Hospital of Philadelphia, Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, 3012 CTRB, 3501 Civic Center Blvd., Philadelphia, PA, 19104, USA.
Stephan A
SA
Grupp
Division of Oncology, The Children's Hospital of Philadelphia, Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, 3012 CTRB, 3501 Civic Center Blvd., Philadelphia, PA, 19104, USA. maude@email.chop.edu.
Shannon L
SL
Maude
D018941:Antigens, CD19 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D064987:Cell- and Tissue-Based Therapy / Q000379:methods; D002986:Clinical Trials as Topic; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D016896:Treatment Outcome
D018941:Antigens, CD19; D000951:Antigens, Neoplasm; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins
Acute lymphoblastic leukemia; CD19; Cellular immunotherapy; Chimeric antigen receptor; Chronic lymphocytic leukemia; Cytokine release syndrome; Engineered T cells