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Cellular Immunotherapy in Lymphoma: Beyond CART Cells

Opinion statement

Cellular immunotherapy has been rapidly evolving and increasingly utilized in the management of relapsed and refractory lymphoma. CD19-specific chimeric antigen receptor T cells (CARTs) have achieved impressive results in pivotal clinical trials. Although CART development continues, these products have fundamental limitations that may make them less desirable in particular settings. For example, CARTs can only target cell surface antigens and thus are incapable of targeting intracellular tumor-associated proteins. In contrast to CARTs, conventional T cell receptors (TCR) allow T cells to target any cellular antigen, including intracellular proteins, since they interact with peptides presented by MHC I and II molecules. T cells recognizing EBV antigens through native TCRs have been successfully employed for treatment and prophylaxis of EBV-associated lymphomas, including post-transplant lymphoproliferative disorder. Currently, transgenic TCR-transduced T cells targeting nonviral tumor antigens remain experimental but, if successful, could become an invaluable cellular therapy option. Because the manufacturing process of autologous T cell products, including CARTs and other tumor-specific T cells, takes several weeks, patients often need bridging therapy to maintain disease control, which may be challenging. Novel cellular platforms, such as genetically modified NK and NKT cells, may be amenable to allogeneic use and thus may allow production as a readily available, “off-the-shelf” product. As cellular therapies beyond CART continue to grow, available therapeutic options for relapsed and refractory lymphoma patients are expected to expand further.

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Funding

This work was supported in part by grants from the Leukemia and Lymphoma Society Specialized Center of Research (grant 7018) and the National Institutes of Health National Cancer Institute (grant 3P50CA126752). MG has research funding from the National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases (5T32DK060445).

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Correspondence to Carlos A. Ramos MD.

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Mahmoud R. Gaballa declares that he has no conflict of interest.

Carlos A. Ramos has received compensation from Novartis and Celgene for service on advisory boards and has received research funding from Tessa Therapeutics.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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Gaballa, M.R., Ramos, C.A. Cellular Immunotherapy in Lymphoma: Beyond CART Cells. Curr. Treat. Options in Oncol. 21, 21 (2020). https://doi.org/10.1007/s11864-020-0709-3

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Keywords

  • Lymphoma
  • Cellular therapy
  • Immunotherapy
  • EBV
  • EBVSTs
  • CART
  • T cells
  • NKT cells
  • DLI
  • CTL
  • Tumor antigens
  • Neoantigens
  • Transgenic TCR
  • Adoptive cell therapy
  • Tumor-specific T cells