Tandem CAR-T cells targeting MUC1 and PSCA combined with anti-PD-1 antibody exhibit potent preclinical activity against non-small cell lung cancer

Wang, Aying; Lv, Tangfeng; Song, Yong

doi:10.1016/j.cellimm.2023.104760

Cited by 8 publications

(8 citation statements)

References 39 publications

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“…Multiple studies have demonstrated that the utilization of immune checkpoint inhibitors in conjunction with CAR-T cells can enhance their cytotoxicity against tumor cells, reverse the depletion of CAR-T cells, and augment their persistence. 9 , 58 , 59 Adachi et al 23 introduced the genes encoding IL-7 and CCL19 receptors into the intracellular domain of CAR, enabling the release of IL-7 and CCL19 upon CAR-T cell activation. This innovative design enhances the durability and infiltration capacity of CAR-T cells within solid tumors.…”

Section: Discussionmentioning

confidence: 99%

“… 5 An increasing number of researchers are currently investigating the mechanisms underlying these barriers and putting forth numerous significant strategies. 6 These strategies encompass further optimizing CAR structure, remodeling TME, 7 targeting inhibitors in TME (e.g., immune checkpoints, chemokine-receptor networks, and immunosuppressive cells), 8 combining immune checkpoint inhibitors, 9 , 10 combining chemotherapy, 11 and combining radiotherapy. 12 , 13 Currently, although CAR-T cells exhibit lower effectiveness in solid tumors compared to hematological malignancies, 14 it is anticipated that once these obstacles are overcome, CAR-T cells will undergo a significant advancement in the treatment of solid tumors.…”

Section: Introductionmentioning

confidence: 99%

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Global research trends in CAR-T cell therapy for solid tumors: A comprehensive visualization and bibliometric study (2012–2023)

Miao,

Zhang,

et al. 2024

Human Vaccines & Immunotherapeutics

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CAR-T cell therapy has emerged as a significant approach for the management of hematological malignancies. Over the past few years, the utilization of CAR-T cells in the investigation and treatment of solid tumors has gained momentum, thereby establishing itself as a prominent area of research. This descriptive study involved the retrieval of articles about CAR-T cell therapy for solid tumors from the Web of Science Core Collection (WoSCC) database. Subsequently, bibliometric analysis and knowledge map analysis were conducted on these articles. The field under consideration is currently experiencing a period of swift advancement, as evidenced by the escalating number of publications in this domain each year. The United States holds an indisputable position as the foremost leader in this particular field, with the University of Pennsylvania emerging as the most active institution. The authors with the highest citation frequency and co-citation frequency are Carl H. June and Shannon L. Maude, respectively. The research hotspots in this field mainly focus on five aspects. Additionally, 10 emerging themes were identified. This study undertakes a comprehensive, systematic, and objective analysis and exploration of the field of CAR-T cell treatment for solid tumors, utilizing bibliometric methods. The findings of this study are expected to serve as a valuable reference and enlightenment for future research endeavors in this particular domain.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Global research trends in CAR-T cell therapy for solid tumors: A comprehensive visualization and bibliometric study (2012–2023)

Miao,

Zhang,

et al. 2024

Human Vaccines & Immunotherapeutics

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“… [ 146 ] Tandem (Tan) CAR-T targeting MUC1 and PSCA Tan CAR T cell therapy has therapeutic effect in NSCLC and has a preclinical rationale for combination with anti-PD-1 antibody. [ 147 ] CAR-NK-92 cells PSCA CAR-NK-92 cells show good anti-tumor effect on PSCA+ tumor cells both in vitro and in vivo , and has the potential to be a therapeutic strategy for cervical cancer. [ 148 ] α-RIT with 211 At-labeled anti-PSCA A11 minibody α-radioimmunotherapy (RIT) with astatine 211-labeled anti-PSCA A11 minibody, showed strong growth inhibition on both macrotumors and intratibial microtumors and promising treatment for micro metastatic and minimal residual disease of prostate cancer.…”

Section: Discussionmentioning

confidence: 99%

Significance of PSCA as a novel prognostic marker and therapeutic target for cancer

Nayerpour Dizaj,

Doustmihan,

Sadeghzadeh Oskouei

et al. 2024

Cancer Cell Int

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One of the contributing factors in the diagnosis and treatment of most cancers is the identification of their surface antigens. Cancer tissues or cells have their specific antigens. Some antigens that are present in many cancers elicit different functions. One of these antigens is the prostate stem cell antigen (PSCA) antigen, which was first identified in the prostate. PSCA is a cell surface protein that has different functions in different tissues. It can play an inhibitory role in cell proliferation as well as a tumor-inducing role. PSCA has several genetic variants involved in cancer susceptibility in some tissues, so identifying the characteristics of this antigen and its relationship with clinical features can provide more information on diagnosis and treatment of patients with cancers. Most studies on the PSCA have focused on prostate cancer. While it is also expressed in other cancers, little attention has been paid to its role as a valuable diagnostic, prognostic, and therapeutic tool in other cancers. PSCA has several genetic variants that seem to play a significant role in cancer susceptibility in some tissues, so identifying the characteristics of this antigen and its relationship and variants with clinical features can be beneficial in concomitant cancer therapy and diagnosis, as theranostic tools. In this study, we will review the alteration of the PSCA expression and its polymorphisms and evaluate its clinical and theranostics significance in various cancers.

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“…Currently, CAR-T cell therapy has shown some advancements in targeting specific antigens such as PD-L1, EGFR, MUC1, MSLN, and PSCA in lung cancer treatment. 23 , 45 However, NEDD1 has exhibited resistance to most CAR-T cell therapies. In conclusion, we posit that NEDD1-dependent LUAD lacks the requisite therapeutic targets for neoadjuvant chemotherapy, and the presence of tolerance to ICIs and CAR-T cell therapies further exacerbates LUAD resistance.…”

Section: Discussionmentioning

confidence: 99%

NEDD1 overexpression increases cell proliferation, tumor immune escape, and drug resistance in LUAD

Zhuo,

Wu,

Chen

et al. 2024

J. Cancer

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Background: Neural Precursor Cell Expressed Developmentally Down-Regulated Protein 1 (NEDD1) serves as a crucial factor in promoting cellular mitosis by directly facilitating wheel assembly and daughter centriole biogenesis at the lateral site of parent centrioles, ultimately driving centrosome replication. The amplification of centrosomes and the abnormal expression of centrosome-associated proteins contribute to the invasion and metastasis of non-small cell lung cancer cells. However, the specific mechanism by which NEDD1 contributes to the progression of lung adenocarcinoma (LUAD) remains unexplored. Therefore, the objective of this study is to uncover the role played by NEDD1 in LUAD. Methods: To verify the expression of NEDD1 in pan-carcinoma. The feasibility of NEDD1 as a prognostic marker for LUAD in TCGA and GEO databases was verified. Subsequently, Cox proportional hazard regression analysis was used to screen the prognostic factors of LUAD, so as to analyze the correlation between prognostic factors and NEDD1 expression. For another, NEDD1-related genes were screened for pathway enrichment analysis to verify their possible functions. In addition, the expression of NEDD1 in LUAD was verified by qPCR and IHC, then siRNA was used to construct NEDD1-knocked lung cancer cells for subsequent cytobehavioral experiments. Finally, the distribution of NEDD1 in single-cell samples was revealed, and then the correlation between its overexpression and LUAD immune escape and drug resistance was analyzed. Results: LUAD exhibits upregulation of NEDD1, which in turn promotes the proliferation, migration, invasion, and epithelial-mesenchymal transition of lung cancer cells, thereby contributing to a poor prognosis. Furthermore, the overexpression of NEDD1 is closely associated with immune escape and drug resistance in LUAD. Conclusion: NEDD1 serves as a reliable prognostic marker for LUAD, and its upregulation is associated with increased immune escape and drug resistance. Given these findings, NEDD1 holds potential as a novel therapeutic target for the treatment of LUAD.

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Tandem CAR-T cells targeting MUC1 and PSCA combined with anti-PD-1 antibody exhibit potent preclinical activity against non-small cell lung cancer

Cited by 8 publications

References 39 publications

Global research trends in CAR-T cell therapy for solid tumors: A comprehensive visualization and bibliometric study (2012–2023)

Global research trends in CAR-T cell therapy for solid tumors: A comprehensive visualization and bibliometric study (2012–2023)

Significance of PSCA as a novel prognostic marker and therapeutic target for cancer

NEDD1 overexpression increases cell proliferation, tumor immune escape, and drug resistance in LUAD

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