CAR-T cell therapy in ovarian cancer: from the bench to the bedside

Zhu, Xin‐Xin; Cai, Han; Zhao, Ling; Li, Ning; Lang, Jinghe

doi:10.18632/oncotarget.19929

Cited by 52 publications

(38 citation statements)

References 129 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There are indeed knowledge gaps in research, such as how to reduce the CRS, improve homing, and keep consistency in OC patients. Previously, some researchers had proposed that selecting target antigens with high specificity, optimizing the function of CAR-T cells, and blocking immunosuppressive molecules such as PD1/ PDL1 signal, could reduce the occurrence of CRS [33][34][35][36][37]. Moreover, combining higher specific CAR-T cells with chemokine receptors may improve homing and enhance therapeutic activity [6].…”

Section: Discussionmentioning

confidence: 99%

Therapeutic effect of dual CAR-T targeting PDL1 and MUC16 antigens on ovarian cancer cells in mice

Wang

2020

BMC Cancer

View full text Add to dashboard Cite

Background: More favorable treatment against epithelial ovarian cancer (EOC) is urgently needed because of its insidious nature at an early stage and a low rate of five-year survival. The current primary treatment, extensive surgery combined with chemotherapy, exhibits limited benefits for improving prognosis. Chimeric antigen receptor T (CAR-T) cell technology as novel immunotherapy has made breakthrough progress in the treatment of hematologic malignancies, and there were also benefits shown in a partial solid tumor in previous research. Therefore, CART cell technology may be a promising candidate as an immunotherapeutic tool against EOC. However, there are some weaknesses in targeting one antigen from the previous preclinical assay, such as ontarget off-tumor cytotoxicity. The dual-target CART cell may be a better choice. Methods: We constructed tandem PD1-antiMUC16 dual-CAR, PD1 single-CAR, and anti-MUC16 single-CAR fragments by PCR and genetic engineering, followed by preparing CART cells via lentiviral infection. The expression of CAR molecules on single and dual CART cells was detected by flow cytometry. The killing capacity and activation of CART cells were measured by cytotoxic assays and cytokines release assays in vitro. The therapeutic capacity of CART cells was assessed by tumor-bearing mice model assay in vivo. Results: We successfully constructed CARs lentiviral expression vectors and obtained single and dual CART cells. CART cells demonstrated robust killing capacity against OVCAR-3 cells in vitro. Meanwhile, CART cells released plenty of cytokines such as interleukin-2(IL-2), interferon-γ (IFN-γ) and tumor necrosis factor-α(TNF-α). CART cells showed a therapeutic benefit against OVCAR-3 tumor-bearing mice and significantly prolonged the survival time. Dual CART cells were shown to be two to four times more efficacious than single CART cells in terms of survival time. Conclusion: Although exhibiting a similar ability as single CART cells against OVCAR-3 cells in vitro, dual CART cells demonstrated enhanced killing capacity against OVCAR-3 cells as compared to single CART cells in vivo and significantly prolonged the survival time of tumor-bearing mice. PD1-antiMUC16 CART cells showed more potent antitumor activity than single CART cells in vivo. The present experimental data may support further research work that will have the potential to lead to clinical studies.

show abstract

Section: Discussionmentioning

confidence: 99%

Therapeutic effect of dual CAR-T targeting PDL1 and MUC16 antigens on ovarian cancer cells in mice

Wang

2020

BMC Cancer

View full text Add to dashboard Cite

show abstract

“…Ovarian cancer tumor cells often evade destruction by CTLs through inhibitory signals in the tumor ( 48 ). Mucin 16, α-folate receptor, and mesothelin are being investigated as specific targets of genetic modification of chimeric antigen receptor T (CAR-T) cell therapies for ovarian cancer ( 49 ). Oncolytic viral therapy that utilizes genetic engineering is also being used to create viruses that selectively infect tumor cells and lead to tumor cell lysis ( 11 ).…”

Section: Current State Of Ovarian Cancer Immunotherapymentioning

confidence: 99%

Immunotherapy for Ovarian Cancer: Adjuvant, Combination, and Neoadjuvant

et al. 2020

View full text Add to dashboard Cite

Ovarian cancer is the most lethal gynecologic malignancy. Surgery and chemotherapy are the primary treatments for ovarian cancer; however, patients often succumb to recurrence with chemotherapeutic resistance within several years after the initial treatment. In the past two decades, immunotherapy has rapidly developed, and has revolutionized the treatment of various types of cancer. Despite the fact that immunotherapy response rates among ovarian cancer patients remain modest, treatment with immune checkpoint inhibitors (ICIs), chimeric antigen receptor (CAR)- and TCR-engineered T cells is rapidly developing. Therapeutic efficiency could be improved significantly if immunotherapy is included as an adjuvant therapy, in combination with chemotherapy, radiation therapy, and the use of anti-angiogenesis drugs, and poly ADP ribose polymerase inhibitors (PARPi). Newly developed technologies that identify therapeutic targets, predict treatment efficacy, rapidly screen potential immunotherapy drugs, provide neoadjuvant immunotherapy, and utilize nanomedicine technology provide new opportunities for the treatment of ovarian cancer, and have the potential to prolong patient survival. However, important issues that may hinder the efficacy of such approaches, including hyperprogressive disease (HPD), immunotherapy-resistance, and toxicity of the treatments, including neurotoxicity, must be taken into account and addressed for these therapies to be effective.

show abstract

“…For detailed reviews of antibody-based immunotherapies for ovarian cancer see Tse et al, 2014 [ 200 ] and Drerup et al, 2015 [ 201 ]. For more recent reviews of immune therapies for ovarian cancer with engineered T-cells, TCRs, and CAR-T cells see Marth et al, 2019 [ 8 ]; Fan et al, 2018 [ 53 ]; Rodriguez et al, 2018 [ 73 ]; Zhu et al, 2017 [ 202 ]; Rodriguez-Garcia et al, 2017 [ 203 ]; Gaillard et al, 2016 [ 52 ]; Alipour et al, 2016 [ 204 ]. These include summaries of recruiting and ongoing clinical trials targeting immune checkpoint inhibitors or various antigens including, NY-ESO-1, HER2, FR-alpha, MSLN, MUC16 (CA125), EGFR, CD133, CEA, NKG2D, MAGE-A4, WT-1, and p53.…”

Section: Agents and Strategies For Cancer Immunotherapymentioning

confidence: 99%

Epithelial Ovarian Cancer and the Immune System: Biology, Interactions, Challenges and Potential Advances for Immunotherapy

Macpherson

Barry

Ricciardelli

et al. 2020

JCM

View full text Add to dashboard Cite

Recent advances in the understanding of immune function and the interactions with tumour cells have led to the development of various cancer immunotherapies and strategies for specific cancer types. However, despite some stunning successes with some malignancies such as melanomas and lung cancer, most patients receive little or no benefit from immunotherapy, which has been attributed to the tumour microenvironment and immune evasion. Although the US Food and Drug Administration have approved immunotherapies for some cancers, to date, only the anti-angiogenic antibody bevacizumab is approved for the treatment of epithelial ovarian cancer. Immunotherapeutic strategies for ovarian cancer are still under development and being tested in numerous clinical trials. A detailed understanding of the interactions between cancer and the immune system is vital for optimisation of immunotherapies either alone or when combined with chemotherapy and other therapies. This article, in two main parts, provides an overview of: (1) components of the normal immune system and current knowledge regarding tumour immunology, biology and their interactions; (2) strategies, and targets, together with challenges and potential innovative approaches for cancer immunotherapy, with attention given to epithelial ovarian cancer.

show abstract

CAR-T cell therapy in ovarian cancer: from the bench to the bedside

Cited by 52 publications

References 129 publications

Therapeutic effect of dual CAR-T targeting PDL1 and MUC16 antigens on ovarian cancer cells in mice

Therapeutic effect of dual CAR-T targeting PDL1 and MUC16 antigens on ovarian cancer cells in mice

Immunotherapy for Ovarian Cancer: Adjuvant, Combination, and Neoadjuvant

Epithelial Ovarian Cancer and the Immune System: Biology, Interactions, Challenges and Potential Advances for Immunotherapy

Contact Info

Product

Resources

About