Dual CAR-T cells to treat cancers co-expressing NKG2D and PD1 ligands in xenograft models of peritoneal metastasis

Jiang, Guangyi; Ng, Yi Zhen; Tay, Johan Chin-Kang; Du, Zhicheng; Xiao, Lin; Wang, Shu; Zhu, Jianqing

doi:10.1007/s00262-022-03247-9

Cited by 12 publications

(9 citation statements)

References 32 publications

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“…Knowledge of the subpopulation makeup of CAR T cell products is typically complemented by the quantification of expression of exhaustion markers, PD-1, TIGIT, LAG3, and TIM3 [ 27 , 28 ]. Notably, although PD-1 expression on T cells has been strongly associated with a lack of therapeutic effects [ 29 , 30 ], it can also be a marker of recent T cell activation [ 31 ]. Therefore, the simultaneous expression of several exhaustion markers appears to be a more reliable marker of genuinely exhausted T cells.…”

Section: Resultsmentioning

confidence: 99%

Comparative Pre-Clinical Analysis of CD20-Specific CAR T Cells Encompassing 1F5-, Leu16-, and 2F2-Based Antigen-Recognition Moieties

Belovezhets

Kulemzin

Volkova

et al. 2023

IJMS

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Over the past decade, CAR T cell therapy for patients with B cell malignancies has evolved from an experimental technique to a clinically feasible option. To date, four CAR T cell products specific for a B cell surface marker, CD19, have been approved by the FDA. Despite the spectacular rates of complete remission in r/r ALL and NHL patients, a significant proportion of patients still relapse, frequently with the CD19 low/negative tumor phenotype. To address this issue, additional B cell surface molecules such as CD20 were proposed as targets for CAR T cells. Here, we performed a side-by-side comparison of the activity of CD20-specific CAR T cells based on the antigen-recognition modules derived from the murine antibodies, 1F5 and Leu16, and from the human antibody, 2F2. Whereas CD20-specific CAR T cells differed from CD19-specific CAR T cells in terms of subpopulation composition and cytokine secretion, they displayed similar in vitro and in vivo potency.

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Section: Resultsmentioning

confidence: 99%

Comparative Pre-Clinical Analysis of CD20-Specific CAR T Cells Encompassing 1F5-, Leu16-, and 2F2-Based Antigen-Recognition Moieties

Belovezhets

Kulemzin

Volkova

et al. 2023

IJMS

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Section: Target Antigens For Ovarian Cancer Car-t Therapymentioning

confidence: 99%

“…Despite the fact that various studies reported the expression of NKG2DL or PD-L1 in numerous types of oncological indications, whether the simultaneous expression of these two antigens is present in different tumors is less explored ( 129 ). In this regard, Jiang and colleagues investigated the expression of NKG2DL and PD-L1 in human ovarian cancer tissue samples and demonstrated that almost 80% of the samples exhibited the co-expression of the mentioned antigens ( 129 ). Briefly, these researchers designed a unique dual CAR circuit that was based on two separate CAR constructs; one based on the extracellular domain of NKG2D fused to the DAP12 activation domain (which provides the principal activation signals), and the other based on a high-affinity PD-L1-specific scFv fused to the co-stimulatory domain of 4-1BB (which provides auxiliary signals necessary for efficient activation of CAR-Ts following antigen encounter) ( 129 ).…”

Section: Target Antigens For Ovarian Cancer Car-t Therapymentioning

confidence: 99%

CAR-T cell immunotherapy for ovarian cancer: hushing the silent killer

Nasiri,

Farrokhi,

Safarzadeh Kozani

et al. 2023

Front. Immunol.

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As the most lethal gynecologic oncological indication, carcinoma of the ovary has been ranked as the 5th cause of cancer-related mortality in women, with a high percentage of the patients being diagnosed at late stages of the disease and a five-year survival of ~ 30%. Ovarian cancer patients conventionally undergo surgery for tumor removal followed by platinum- or taxane-based chemotherapy; however, a high percentage of patients experience tumor relapse. Cancer immunotherapy has been regarded as a silver lining in the treatment of patients with various immunological or oncological indications; however, mirvetuximab soravtansine (a folate receptor α-specific mAb) and bevacizumab (a VEGF-A-specific mAb) are the only immunotherapeutics approved for the treatment of ovarian cancer patients. Chimeric antigen receptor T-cell (CAR-T) therapy has achieved tremendous clinical success in the treatment of patients with certain B-cell lymphomas and leukemias, as well as multiple myeloma. In the context of solid tumors, CAR-T therapies face serious obstacles that limit their therapeutic benefit. Such hindrances include the immunosuppressive nature of solid tumors, impaired tumor infiltration, lack of qualified tumor-associated antigens, and compromised stimulation and persistence of CAR-Ts following administration. Over the past years, researchers have made arduous attempts to apply CAR-T therapy to ovarian cancer. In this review, we outline the principles of CAR-T therapy and then highlight its limitations in the context of solid tumors. Ultimately, we focus on preclinical and clinical findings achieved in CAR-T-mediated targeting of different ovarian cancer-associated target antigens.

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“…Targeting multiple antigens and application of novel CAR can improve the targeting of CAR-T cells. Jiang and colleagues constructed a dual CAR system containing two extracellular domains, NKG2D and PD-1, and showed that such CAR-T cells effectively eliminated target cancer cells ( 90 ). CAR-T cells that dual target CD30 and CEA have a more specific ability to kill tumor cells, which is manifested by blocking the inhibition of cytotoxic T lymphocyte immune function induced by CD30 ( 27 ).…”

Section: Strategiesmentioning

confidence: 99%

Recent advances in CAR-T cells therapy for colorectal cancer

Qin

Chen

et al. 2022

Front. Immunol.

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Colorectal cancer (CRC) is the third most common cancer, with a high mortality rate and a serious impact on people’s life and health. In recent years, adoptive chimeric antigen receptor T (CAR-T) cells therapy has shown well efficacy in the treatment of hematological malignancies, but there are still many problems and challenges in solid tumors such as CRC. For example, the tumor immunosuppressive microenvironment, the low targeting of CAR-T cells, the short time of CAR-T cells in vivo, and the limited proliferation capacity of CAR-T cells, CAR-T cells can not effectively infiltrate into the tumor and so on. New approaches have been proposed to address these challenges in CRC, and this review provides a comprehensive overview of the current state of CAR-T cells therapy in CRC.

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Dual CAR-T cells to treat cancers co-expressing NKG2D and PD1 ligands in xenograft models of peritoneal metastasis

Cited by 12 publications

References 32 publications

Comparative Pre-Clinical Analysis of CD20-Specific CAR T Cells Encompassing 1F5-, Leu16-, and 2F2-Based Antigen-Recognition Moieties

Comparative Pre-Clinical Analysis of CD20-Specific CAR T Cells Encompassing 1F5-, Leu16-, and 2F2-Based Antigen-Recognition Moieties

CAR-T cell immunotherapy for ovarian cancer: hushing the silent killer

Recent advances in CAR-T cells therapy for colorectal cancer

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