Harnessing the potential of CAR-T cell therapy: progress, challenges, and future directions in hematological and solid tumor treatments

Dagar, Gunjan; Gupta, Ashna; Masoodi, Tariq; Nisar, Sabah; Merhi, Maysaloun; Hashem, Sheema; Chauhan, Ramesh Chand; Dagar, Manisha; Mirza, Sameer; Bagga, Puneet; Kumar, Rakesh; Akil, Ammira S. Al-Shabeeb; Macha, Muzafar A.; Haris, Mohammad; Uddin, Shahab; Singh, Mayank; Bhat, Ajaz A.

doi:10.1186/s12967-023-04292-3

Cited by 50 publications

(23 citation statements)

References 373 publications

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“…Improving the efficacy of CAR-T cells on solid tumors remains an active area of research (Dagar et al, 2023). To investigate whether the BT-474-Luc2 line could be used as a reporter of HER2 CAR-T cell targeting, cytotoxicity of HER2 CAR-T cells on BT-474-Luc2 cells was measured by luminescence.…”

Section: Optimizing Ex Vivo Her2 Car-t Cell-mediated Cytotoxicity Ass...mentioning

confidence: 99%

Optimizing ex vivo CAR-T cell-mediated cytotoxicity assay through multimodality imaging

Foulke,

Chen,

Chang

et al. 2024

Preprint

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CAR-T cell-based therapies have demonstrated remarkable efficacy in treating malignant cancers, especially liquid tumors, and are increasingly being evaluated in clinical trials for solid tumors. With the FDA's initiative for advancing alternative methods for drug discovery and development, full human ex vivo assays are increasingly essential for precision CAR-T development. However, prevailing ex vivo CAR-T cell-mediated cytotoxicity assays are limited by their use of radioactive materials, lack of real-time measurement, low throughput, and inability to automate, among others. To address these limitations, we optimized the assay using multimodality imaging methods, including bioluminescence, impedance tracking, phase contrast, and fluorescence, to track CAR-T cells co-cultured with CD19, CD20, and HER2 luciferase reporter cancer cells in real-time. Additionally, we varied the ratio of CAR-T cells to cancer cells to determine optimal cytotoxicity readouts. Our findings demonstrated that the CAR-T cell group effectively attacked cancer cells, and the optimized assay provided superior temporal and spatial precision measurements of ex vivo CAR-T killing of cancer cells, confirming the reliability, consistency, and high throughput of the optimized assay.

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Section: Optimizing Ex Vivo Her2 Car-t Cell-mediated Cytotoxicity Ass...mentioning

confidence: 99%

Optimizing ex vivo CAR-T cell-mediated cytotoxicity assay through multimodality imaging

Foulke,

Chen,

Chang

et al. 2024

Preprint

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“…As depicted in Figure 1 , the Achilles’ heels of CAR T-cell therapy, which currently hinder its wider efficacy and acceptance in clinical practice, encompass resistance to CAR-T cell therapy, safety concerns, and manufacturing intricacies ( 26 , 37 , 38 ). One major issue is tumor antigen escape, where cancer cells mutate or downregulate the target antigen recognized by CAR-T cells, leading to treatment resistance and disease relapse ( 37 ).…”

Section: Achilles Heels Of Car T-cell Therapymentioning

confidence: 99%

Charting new paradigms for CAR-T cell therapy beyond current Achilles heels

Li,

Hu,

et al. 2024

Front. Immunol.

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Chimeric antigen receptor-T (CAR-T) cell therapy has made remarkable strides in treating hematological malignancies. However, the widespread adoption of CAR-T cell therapy is hindered by several challenges. These include concerns about the long-term and complex manufacturing process, as well as efficacy factors such as tumor antigen escape, CAR-T cell exhaustion, and the immunosuppressive tumor microenvironment. Additionally, safety issues like the risk of secondary cancers post-treatment, on-target off-tumor toxicity, and immune effector responses triggered by CAR-T cells are significant considerations. To address these obstacles, researchers have explored various strategies, including allogeneic universal CAR-T cell development, infusion of non-activated quiescent T cells within a 24-hour period, and in vivo induction of CAR-T cells. This review comprehensively examines the clinical challenges of CAR-T cell therapy and outlines strategies to overcome them, aiming to chart pathways beyond its current Achilles heels.

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“…Chimeric antigen receptor (CAR) T-cells is a recently advancing approach of immunotherapy for the treatment of solid tumors where antibody fragments are used along with T cells specific against TSAs [173,174]. CAR T-cell therapy have been reported to show a remarkable success in B cell hematological malignancy [175][176][177][178]. There are several newly emerging TAAs under investigation such as immune checkpoint B7-H3 (CD276), Mucin-1, IL-6 receptor (CD126), Lewis-y antigen, STEAP-1 [179].…”

Section: Immunotherapymentioning

confidence: 99%

Recent advances and future perspectives in the therapeutics of prostate cancer

Varaprasad,

Gupta,

Prasad

et al. 2023

Exp Hematol Oncol

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Prostate cancer (PC) is one of the most common cancers in males and the fifth leading reason of death. Age, ethnicity, family history, and genetic defects are major factors that determine the aggressiveness and lethality of PC. The African population is at the highest risk of developing high-grade PC. It can be challenging to distinguish between low-risk and high-risk patients due to the slow progression of PC. Prostate-specific antigen (PSA) is a revolutionary discovery for the identification of PC. However, it has led to an increase in over diagnosis and over treatment of PC in the past few decades. Even if modifications are made to the standard PSA testing, the specificity has not been found to be significant. Our understanding of PC genetics and proteomics has improved due to advances in different fields. New serum, urine, and tissue biomarkers, such as PC antigen 3 (PCA3), have led to various new diagnostic tests, such as the prostate health index, 4K score, and PCA3. These tests significantly reduce the number of unnecessary and repeat biopsies performed. Chemotherapy, radiotherapy, and prostatectomy are standard treatment options. However, newer novel hormone therapy drugs with a better response have been identified. Androgen deprivation and hormonal therapy are evolving as new and better options for managing hormone-sensitive and castration-resistant PC. This review aimed to highlight and discuss epidemiology, various risk factors, and developments in PC diagnosis and treatment regimens.

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Harnessing the potential of CAR-T cell therapy: progress, challenges, and future directions in hematological and solid tumor treatments

Cited by 50 publications

References 373 publications

Optimizing ex vivo CAR-T cell-mediated cytotoxicity assay through multimodality imaging

Optimizing ex vivo CAR-T cell-mediated cytotoxicity assay through multimodality imaging

Charting new paradigms for CAR-T cell therapy beyond current Achilles heels

Recent advances and future perspectives in the therapeutics of prostate cancer

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