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Related Concept Videos

Diversity of Antigen Receptors01:28

Diversity of Antigen Receptors

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Antigen receptors are essential components of the immune system crucial in defending the body against foreign invaders. These receptors are present on the surface of B and T cells, enabling them to recognize antigens and mount an appropriate immune response.
Before encountering any antigen, lymphocytes express these receptors. On B cells, the antigen receptor is a membrane-bound antibody molecule called BCR; on T cells, it is a T cell receptor or TCR. B and T cell receptors are composed of two...
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Chimeric Antigen Receptor T Cells in Refractory B-Cell Lymphomas.

Stephen J Schuster1, Jakub Svoboda1, Elise A Chong1

  • 1From the Lymphoma Program at the Abramson Cancer Center and the Division of Hematology-Oncology (S.J.S., J.S., E.A.C., S.D.N., A.R.M., D.L., D.L.P.), and the Department of Pathology and Laboratory Medicine (V.B., M.W., B.L.L., S.F.L., J.J.M., C.H.J.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Novartis Pharmaceuticals, Basel, Switzerland (Ö.A.); and Novartis Institutes for BioMedical Research, Cambridge, MA (J.L.B., I.P-M.).

The New England Journal of Medicine
|December 12, 2017
PubMed
Summary
This summary is machine-generated.

Chimeric antigen receptor (CAR) T cells targeting CD19 show promise for treating refractory B-cell lymphomas. This study found high durable remission rates in diffuse large B-cell lymphoma and follicular lymphoma patients, despite manageable toxicities.

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Area of Science:

  • Oncology
  • Immunotherapy
  • Hematology

Background:

  • Diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) refractory to standard treatments have poor prognoses.
  • Chimeric antigen receptor (CAR) T-cell therapy targeting CD19 has shown high response rates in B-cell cancers, but data in lymphomas are limited.

Purpose of the Study:

  • To evaluate the efficacy and safety of CD19-directed CAR T cells (CTL019) in adult patients with relapsed or refractory DLBCL or FL.
  • To assess treatment response, toxic effects, CTL019 cell kinetics, and immune recovery.

Main Methods:

  • Autologous T cells engineered to express a CD19-directed CAR (CTL019) were administered to 28 adult patients with relapsed/refractory DLBCL or FL.
  • Patients were monitored for clinical response, adverse events, CAR T-cell expansion and persistence, and immune reconstitution.

Main Results:

  • Overall response rate was 64% (18/28 patients). Complete remission (CR) was achieved in 43% of DLBCL patients and 71% of FL patients.
  • Durable remissions were observed, with 86% of DLBCL responders and 89% of FL responders maintaining response at a median follow-up of 28.6 months.
  • Severe cytokine-release syndrome occurred in 18% of patients, and serious encephalopathy in 11%, with one fatal case.

Conclusions:

  • CTL019 CAR T-cell therapy is effective for treating relapsed or refractory DLBCL and FL, yielding high durable remission rates.
  • While significant toxicities like cytokine-release syndrome and encephalopathy were observed, B-cell and immunoglobulin recovery occurred in some patients.
  • The study highlights the potential of CAR T-cell therapy for aggressive B-cell lymphomas, necessitating careful management of associated toxicities.