The toxicity of cell therapy: Mechanism, manifestations, and challenges

Jin, Yongjia; Dong, Yan; Jin, Zhang; Sun, Jingwei; Liu, Yarong; Chen, Yong

doi:10.1002/jat.4100

Cited by 9 publications

(8 citation statements)

References 79 publications

(108 reference statements)

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“…Rapid developments in the field of antigen identification, gene therapy, and T cell biology have led to the emergence of chimeric antigen receptor T (CAR-T) cell therapy and T cell receptor-engineered T cell (TCR-T) therapy ( 150 , 151 ). Notably, the processes involved in the use of TCR-T and CAR-T for the treatment of pancreatic cancer differ slightly ( 152 ). In TCR-T, the T cells are first collected from patients; they are then selected and the TCR sequence is genetically modified to specifically bind to pancreatic cancer cells.…”

Section: Other Immune-related Therapiesmentioning

confidence: 99%

“…However, a second patient with the same KRAS mutation and human leukocyte antigen allele did not benefit from TCR-T cell therapy. Although the reason for the lack of benefit remains unclear, treatment-related toxicities are a concern with TCR-T therapy ( 150 , 152 ). Its efficacy and the TME requirements warrant further evaluation.…”

Section: Other Immune-related Therapiesmentioning

confidence: 99%

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Frontiers and future of immunotherapy for pancreatic cancer: from molecular mechanisms to clinical application

Zheng,

Liu,

Zhang

et al. 2024

Front. Immunol.

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Pancreatic cancer is a highly aggressive malignant tumor, that is becoming increasingly common in recent years. Despite advances in intensive treatment modalities including surgery, radiotherapy, biological therapy, and targeted therapy, the overall survival rate has not significantly improved in patients with pancreatic cancer. This may be attributed to the insidious onset, unknown pathophysiology, and poor prognosis of the disease. It is therefore essential to identify and develop more effective and safer treatments for pancreatic cancer. Tumor immunotherapy is the new and fourth pillar of anti-tumor therapy after surgery, radiotherapy, and chemotherapy. Significant progress has made in the use of immunotherapy for a wide variety of malignant tumors in recent years; a breakthrough has also been made in the treatment of pancreatic cancer. This review describes the advances in immune checkpoint inhibitors, cancer vaccines, adoptive cell therapy, oncolytic virus, and matrix-depletion therapies for the treatment of pancreatic cancer. At the same time, some new potential biomarkers and potential immunotherapy combinations for pancreatic cancer are discussed. The molecular mechanisms of various immunotherapies have also been elucidated, and their clinical applications have been highlighted. The current challenges associated with immunotherapy and proposed strategies that hold promise in overcoming these limitations have also been discussed, with the aim of offering new insights into immunotherapy for pancreatic cancer.

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Section: Other Immune-related Therapiesmentioning

confidence: 99%

Section: Other Immune-related Therapiesmentioning

confidence: 99%

Frontiers and future of immunotherapy for pancreatic cancer: from molecular mechanisms to clinical application

Zheng,

Liu,

Zhang

et al. 2024

Front. Immunol.

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“…Toxicities directly related to ACT include cytokine release syndrome, encephalopathy, and on-and off-target toxicity. Additional consequences include organ dysfunction secondary to high doses of IL-2 (often administered alongside TIL therapy) and complications secondary to preconditioning lymphodepletion [ (Jin et al, 2021), (Maude et al, 2018)]. Though severe encephalopathy may certainly lead to dysfunction of the HPO axis, no studies evaluating the specific effect on the HPO axis were encountered in this review of the literature.…”

Section: Hypothalamic Pituitary Ovarian Axismentioning

confidence: 99%

Targeted cancer treatment and fertility: effect of immunotherapy and small molecule inhibitors on female reproduction

Bussies

Richards

Rotz

et al. 2022

Reproductive BioMedicine Online

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Targeted cancer therapy is rapidly evolving the landscape of personalized health care. Novel approaches to selectively impeding tumor growth carry significant potential to improve survival outcomes, particularly for reproductive-aged patients harboring treatment refractory disease. Current agents fall within two classes, immunotherapy and small molecule inhibitors, which are collectively divided into the following subclasses: monoclonal antibodies, immunomodulators, adoptive cell therapy, treatment vaccines, kinase inhibitors, proteosome inhibitors, metalloproteinase and heat shock protein inhibitors, and promoters of apoptosis. The short-and long-term effects of these therapies on the female reproductive system are not well understood. As a result, clinicians are rendered unable to appropriately counsel women on downstream effects to their fertility. Data-driven consensus recommendations are desperately needed. This review aims to characterize the impact of targeted cancer therapy on the female hypothalamic-pituitary-ovary axis, direct ovarian function, and conception.

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“…Tumor-infiltrating lymphocytes (TILs) have shown great promise in solid tumors [ 2 – 5 ], but were limited in gynecologic cancer [ 6 – 8 ], and conventional TIL therapy involves high-intensity lymphodepleting preconditioning with chemotherapy along with high-dose IL-2 administration [ 6 , 9 ], which can cause significant toxicity and is only suitable for patients with good performance [ 6 , 10 ] who receive treatment in specialized clinics [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

IL-2-free tumor-infiltrating lymphocyte therapy with PD-1 blockade demonstrates potent efficacy in advanced gynecologic cancer

Guo,

Wang,

Luo

et al. 2024

BMC Med

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Background Tumor-infiltrating lymphocyte (TIL) therapy has been restricted by intensive lymphodepletion and high-dose intravenous interleukin-2 (IL-2) administration. To address these limitations, we conducted preclinical and clinical studies to evaluate the safety, antitumor activity, and pharmacokinetics of an innovative modified regimen in patients with advanced gynecologic cancer. Methods Patient-derived xenografts (PDX) were established from a local recurrent cervical cancer patient. TILs were expanded ex vivo from minced tumors without feeder cells in the modified TIL therapy regimen. Patients underwent low-dose cyclophosphamide lymphodepletion followed by TIL infusion without intravenous IL-2. The primary endpoint was safety; the secondary endpoints included objective response rate, duration of response, and T cell persistence. Results In matched patient-derived xenografts (PDX) models, homologous TILs efficiently reduced tumor size (p < 0.0001) and underwent IL-2 absence in vivo. In the clinical section, all enrolled patients received TIL infusion using a modified TIL therapy regimen successfully with a manageable safety profile. Five (36%, 95% CI 16.3–61.2) out of 14 evaluable patients experienced objective responses, and three complete responses were ongoing at 19.5, 15.4, and 5.2 months, respectively. Responders had longer overall survival (OS) than non-responders (p = 0.036). Infused TILs showed continuous proliferation and long-term persistence in all patients and showed greater proliferation in responders which was indicated by the Morisita overlap index (MOI) of TCR clonotypes between infused TILs and peripheral T cells on day 14 (p = 0.004) and day 30 (p = 0.004). Higher alteration of the CD8+/CD4+ ratio on day 14 indicated a longer OS (p = 0.010). Conclusions Our modified TIL therapy regimen demonstrated manageable safety, and TILs could survive and proliferate without IL-2 intravenous administration, showing potent efficacy in patients with advanced gynecologic cancer. Trial registration NCT04766320, Jan 04, 2021.

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The toxicity of cell therapy: Mechanism, manifestations, and challenges

Cited by 9 publications

References 79 publications

Frontiers and future of immunotherapy for pancreatic cancer: from molecular mechanisms to clinical application

Frontiers and future of immunotherapy for pancreatic cancer: from molecular mechanisms to clinical application

Targeted cancer treatment and fertility: effect of immunotherapy and small molecule inhibitors on female reproduction

IL-2-free tumor-infiltrating lymphocyte therapy with PD-1 blockade demonstrates potent efficacy in advanced gynecologic cancer

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