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<p>Since the first approval of CAR&#xa0;T-cell therapies in 2017, this innovative technology has become an essential treatment option for relapsed/refractory (r/r) non-Hodgkin lymphomas. In particular CD19-targeted CAR&#xa0;T&#xa0;cells, such as tisagenlecleucel (Kymriah; Novartis, Basel, Switzerland) and axicabtagene ciloleucel (Yescarta; Kite, Gilead, Foster City, CA, USA), have demonstrated remarkable response rates in clinical studies, even in chemotherapy-refractory cases. The approval of additional products, such as lisocabtagene maraleucel (Breyanzi; Juno, Bristol Myers Squibb, New York, NY, USA), has expanded the range of available therapies. Simultaneously, bispecific antibodies (bispecific T‑cell engagers, BiTEs) have emerged as an alternative immunotherapeutic approach. Products like mosunetuzumab (Lunsumio, Genentech Roche), glofitamab (Columvi, Genentech Roche, South San Francisco/CA, USA), and epcoritamab (Epkinly, Genmap/AbbVie, Plainsboro/NJ, USA) provide readily available off-the-shelf treatment options. Studies have shown high response rates in r/r B‑cell lymphomas, albeit with side effects such as cytokine release syndrome (CRS). This review focuses on the clinical outcomes of CAR&#xa0;T-cell and BiTE therapies for aggressive B‑cell lymphomas as well as resistance mechanisms such as antigen loss and T‑cell exhaustion. Additionally, optimization strategies, including dual CAR designs, armored CAR&#xa0;T&#xa0;cells, and modulation of the tumor microenvironment, are discussed. Emerging developments, such as trispecific antibodies and epigenetic modifications, hold promise for further enhancing the efficacy of these therapies and achieving sustainable long-term treatment success.</p>

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Entwicklungen bei CAR-T-Zell-Therapien und bispezifischen Antikörpern

  • 期刊论文

  • 发表日期：

    2025年4月15日

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  • Jessica Propp,
  • Hyatt Balke-Want

摘要

Since the first approval of CAR T-cell therapies in 2017, this innovative technology has become an essential treatment option for relapsed/refractory (r/r) non-Hodgkin lymphomas. In particular CD19-targeted CAR T cells, such as tisagenlecleucel (Kymriah; Novartis, Basel, Switzerland) and axicabtagene ciloleucel (Yescarta; Kite, Gilead, Foster City, CA, USA), have demonstrated remarkable response rates in clinical studies, even in chemotherapy-refractory cases. The approval of additional products, such as lisocabtagene maraleucel (Breyanzi; Juno, Bristol Myers Squibb, New York, NY, USA), has expanded the range of available therapies. Simultaneously, bispecific antibodies (bispecific T‑cell engagers, BiTEs) have emerged as an alternative immunotherapeutic approach. Products like mosunetuzumab (Lunsumio, Genentech Roche), glofitamab (Columvi, Genentech Roche, South San Francisco/CA, USA), and epcoritamab (Epkinly, Genmap/AbbVie, Plainsboro/NJ, USA) provide readily available off-the-shelf treatment options. Studies have shown high response rates in r/r B‑cell lymphomas, albeit with side effects such as cytokine release syndrome (CRS). This review focuses on the clinical outcomes of CAR T-cell and BiTE therapies for aggressive B‑cell lymphomas as well as resistance mechanisms such as antigen loss and T‑cell exhaustion. Additionally, optimization strategies, including dual CAR designs, armored CAR T cells, and modulation of the tumor microenvironment, are discussed. Emerging developments, such as trispecific antibodies and epigenetic modifications, hold promise for further enhancing the efficacy of these therapies and achieving sustainable long-term treatment success.