Tumour Escape from CAR-T Cells

Rasche, Leo; Vago, Luca; Mutis, Tuna

doi:10.1007/978-3-030-94353-0_4

Cited by 9 publications

(6 citation statements)

References 40 publications

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“…Therefore, we believe that teclistamab continues to be a valuable treatment option for patients pretreated with ide-cel -a setting with limited therapeutic options. BCMA-loss, as previously described [26][27][28][29][30] may be one potential mechanism for primary resistance to teclistamab after BCMA therapy, although drivers of resistance may be heterogeneous [31]. Interestingly, all four patients with longterm remissions following teclistamab experienced only limited benefit to ide-cel treatment.…”

Section: Discussionmentioning

confidence: 53%

Real-world analysis of teclistamab in 123 RRMM patients from Germany

Riedhammer,

Bassermann,

Besemer

et al. 2024

Leukemia

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Teclistamab, a B-cell maturation antigen (BCMA) × CD3 directed bispecific antibody, has shown high response rates and durable remissions in the MAJESTEC-1 trial in patients with relapsed and refractory multiple myeloma (RRMM). We retrospectively assessed efficacy and tolerability in 123 patients treated at 18 different German centers to determine whether outcome is comparable in the real-world setting. Most patients had triple-class (93%) or penta-drug (60%) refractory disease, 37% of patients had received BCMA-directed pretreatment including idecabtagene vicleucel (ide-cel) CAR-T cell therapy (21/123, 17.1%). With a follow-up of 5.5 months, we observed an overall response rate (ORR) of 59.3% and a median progression-free survival (PFS) of 8.7 months. In subgroup analyses, we found significantly lower ORR and median PFS in patients with extramedullary disease (37%/2.1 months), and/or an ISS of 3 (37%/1.3 months), and ide-cel pretreated patients (33%/1.8 months). Nonetheless, the duration of response in ide-cel pretreated patients was comparable to that of anti-BCMA naive patients. Infections and grade ≥3 cytopenias were the most frequent adverse events. In summary, we found that teclistamab exhibited a comparable efficacy and safety profile in the real-world setting as in the pivotal trial.

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Section: Discussionmentioning

confidence: 53%

Real-world analysis of teclistamab in 123 RRMM patients from Germany

Riedhammer,

Bassermann,

Besemer

et al. 2024

Leukemia

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“…The aforementioned mechanism can be seen in two of the current FDA-approved drugs based on CAR-T cell therapy, i.e., Tisagenlecleucel (used to treat acute lymphoblastic leukemia) and Axicabtagene ciloleucel (used for treating large B cell lymphoma) [192,193]. However, there are some limitations to overcome: there is the possibility of antigen loss, so that patients treated with CAR-T cells may partially express the antigen or may not express it at all [194][195][196]; another problem is the possibility of the expression of the tumor antigen by normal cells [197]. Although the combination of checkpoint inhibitors and CAR-T cell therapy is a new treatment option, this treatment may still be unable to induce efficient T cell infiltration and may lead to cytokine-mediated toxicities that have been reported in several CAR-T cell therapies [198][199][200][201].…”

Section: Cell-based Vaccines: Dendritic Cells (Dcs) Stem Cells and Ch...mentioning

confidence: 99%

Recent Findings on Therapeutic Cancer Vaccines: An Updated Review

Sheikhlary,

Lopez,

Moghimi

et al. 2024

Biomolecules

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Cancer remains one of the global leading causes of death and various vaccines have been developed over the years against it, including cell-based, nucleic acid-based, and viral-based cancer vaccines. Although many vaccines have been effective in in vivo and clinical studies and some have been FDA-approved, there are major limitations to overcome: (1) developing one universal vaccine for a specific cancer is difficult, as tumors with different antigens are different for different individuals, (2) the tumor antigens may be similar to the body’s own antigens, and (3) there is the possibility of cancer recurrence. Therefore, developing personalized cancer vaccines with the ability to distinguish between the tumor and the body’s antigens is indispensable. This paper provides a comprehensive review of different types of cancer vaccines and highlights important factors necessary for developing efficient cancer vaccines. Moreover, the application of other technologies in cancer therapy is discussed. Finally, several insights and conclusions are presented, such as the possibility of using cold plasma and cancer stem cells in developing future cancer vaccines, to tackle the major limitations in the cancer vaccine developmental process.

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“…Researchers are currently improving CAR-T cell function through a variety of approaches, such as regulating T cell migration by expressing CXCL9 on CAR-T cells, inhibiting tumor angiogenesis, and enhancing the ability of CAR-T cells to recruit T cells [33] . Expression of CXCR2 on CAR-T cells also improves migration and accumulation of CAR-T cells inside tumors, and co-expression of IL-15 and IL-18 inhibits T cell exhaustion and apoptosis [34] .…”

Section: Insufficient Efficiency Of Car-t Cell Trafficking and Infilt...mentioning

confidence: 99%

Application and progress of CAR therapy on malignances: from CAR-T to CAR-NK

Zhang

2024

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For some malignances that are highly aggressive and metastatic are usually considered incurable. However, with the advent of immunotherapy, this therapy could be possibly effective after other three major therapies: surgery, radiation, chemotherapy. As an emerging immunotherapy, chimeric antigen receptor (CAR) T cells have been applied to treat hematologic malignances and some patients achieved long-term remission and temporary cure. However, CAR-T cells also bring side effects such as cytokine release syndrome (CRS), neurotoxicity, etc. Moreover, CAR-T cells did not perform well in solid tumors, for the reason that CAR-T cells are difficult to break through external barrier of solid tumors, at the same time maintain cytotoxicity and persistence inside. Therefore, we introduce CAR-NK cells therapy on the basis of CAR-T cells. At present all CAR-NK cell therapies are in clinical trials, its effectiveness has been initially observed. Compared with CAR-T cells, patients with hematologic malignances received CAR-NK cell therapies showed few side effects such as CRS and neurotoxicity.

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Tumour Escape from CAR-T Cells

Cited by 9 publications

References 40 publications

Real-world analysis of teclistamab in 123 RRMM patients from Germany

Real-world analysis of teclistamab in 123 RRMM patients from Germany

Recent Findings on Therapeutic Cancer Vaccines: An Updated Review

Application and progress of CAR therapy on malignances: from CAR-T to CAR-NK

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