What are the new indications under investigation for chimeric antigen receptor (CAR) T-cell therapy?

Updated: Dec 17, 2020
  • Author: Sameh Gaballa, MD, MS; Chief Editor: Emmanuel C Besa, MD  more...
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The field of CAR T-cell therapy continues to grow, with new data and indications, and more approvals are expected in the near future. The field is moving beyond lymphoid malignancies, and many trials in other hematological malignancies and solid tumors are ongoing. At the time of this writing, 288 clinical trials that are currently recruiting patients are listed on clinicaltrials.gov. Some of these address limitations of anti-CD19 therapy, while others expand CAR T-cell therapy to other indications.

Novel CAR T constructs targeting more than one antigen are now in late clinical stages, with clinical data generated. For example, dual CD19- and CD22-targeting CAR T-cell constructs are showing early promise in ALL and DLBCL, including cases in which a CD19-targeting CAR T-cell product had previously failed. [46, 4, 47]  Other similar concepts include anti-myeloma CAR T constructs targeting more than one antigen on myeloma cells. In addition, initial research suggests that use of CAR T cells that target both CD19 and CD123, another antigen commonly found on leukemia cells, may prevent antigen loss. [48]

Allogeneic CAR T constructs are also in clinical trials and would theoretically offer an ‘off-the-shelf” product that would simplify the process of delivering CAR T therapy, particularly in patients with rapidly progressive disease who cannot wait several weeks for autologous CAR T manufacturing. Early phase I data in DLBCL and follicular lymphoma have been presented, but more data are needed to determine how efficacious these products will be compared with autologous CAR T constructs. [49]

In summary, current CAR T-cell therapies represent a major advance in the treatment of B-cell malignancies as well as a new paradigm for future efforts directed at other currently incurable tumor types. CAR T cell use can be associated with severe and even life-threatening side effects, but these toxicities must be viewed in the context of the risk-benefit ratio. Fortunately, with experience, these toxicities can be ameliorated. One may reasonably hope that over the next few years, new and effective applications of this exciting treatment modality will expand to more cancers.

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