Enhanced AC133-specific CAR T cell therapy induces durable remissions in mice with metastatic small cell lung cancer

Taromi, Sanaz; Firat, Elke; Simonis, Alexander; Braun, Lukas; Apostolova, Petya; Elze, Mirjam; Passlick, Bernward; Schumacher, Alicia; Lagies, Simon; Frey, Axel W.; Schmitt‐Graeff, Annette; Burger, Meike; Schmittlutz, Katrin; Follo, Marie; Elverfeldt, Dominik von; Zhu, Xuekai; Kammerer, Bernd; Diederichs, Sven; Duyster, Justus; Manz, Markus G.; Niedermann, Gabriele; Zeiser, Robert

doi:10.1016/j.canlet.2022.215697

Cited by 20 publications

(11 citation statements)

References 40 publications

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“…After preconditioning chemotherapy, which is routinely given prior to CAR T cell infusion, our SC16.8_mIL18 CAR T cells induced long-term remission in an aggressive immunocompetent metastatic mSCLC model. A recent study describes CAR T cells targeting AC133 on chemotherapy-resistant SCLC stem cells in combination with ICB and CD73 inhibition ( 26 ). This triple combination was effective in a xenograft SCLC model, but its activity has not yet been reported in a representative syngeneic mouse model.…”

Section: Discussionmentioning

confidence: 99%

IL-18–secreting CAR T cells targeting DLL3 are highly effective in small cell lung cancer models

Jaspers¹,

Khan²,

Godfrey³

et al. 2023

Journal of Clinical Investigation

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Kowa, Lilly, Merck, and Syros. He serves on the scientific advisory boards of Bridge Medicines, Earli, and Harpoon Therapeutics. RJB has licensed intellectual property to and collect royalties from BMS, Caribou and Sanofi and received research funding from BMS. RJB is a consultant to BMS, Atara Biotherapeutics Inc, Coimmune, Triumvira and was a consultant for Gracell Biotechnologies Inc but ended employment in the past 24 months. RJB is a member of the scientific advisory board for CoImmune and Triumvira, and has ownership interest (including patents) in IL-18. No potential conflicts of interest were disclosed by the other authors.

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Section: Discussionmentioning

confidence: 99%

IL-18–secreting CAR T cells targeting DLL3 are highly effective in small cell lung cancer models

Jaspers¹,

Khan²,

Godfrey³

et al. 2023

Journal of Clinical Investigation

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“…Sanaz Taromi et al. reported that the combined therapy of CAR-T cells, anti-PD-1-antibody, and CD73 inhibitor can specifically eliminate chemo-resistant tumor stem cells and overcome SCLC-mediated T-cell inhibition in a humanized orthotopic SCLC mouse model ( 129 ).…”

Section: Discussionmentioning

confidence: 99%

Research progress of biomarkers in the prediction of anti-PD-1/PD-L1 immunotherapeutic efficiency in lung cancer

et al. 2023

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Currently, anti-PD-1/PD-L1 immunotherapy using immune checkpoint inhibitors is widely used in the treatment of multiple cancer types including lung cancer, which is a leading cause of cancer death in the world. However, only a limited proportion of lung cancer patients will benefit from anti-PD-1/PD-L1 therapy. Therefore, it is of importance to predict the response to immunotherapy for the precision treatment of patients. Although the expression of PD-L1 and tumor mutation burden (TMB) are commonly used to predict the clinical response of anti-PD-1/PD-L1 therapy, other factors such as tumor-specific genes, dMMR/MSI, and gut microbiome are also promising predictors for immunotherapy in lung cancer. Furthermore, invasive peripheral blood biomarkers including blood DNA-related biomarkers (e.g., ctDNA and bTMB), blood cell-related biomarkers (e.g., immune cells and TCR), and other blood-related biomarkers (e.g., soluble PD-L1 and cytokines) were utilized to predict the immunotherapeutic response. In this review, the current achievements of anti-PD-1/PD-L1 therapy and the potential biomarkers for the prediction of anti-PD-1/PD-L1 immunotherapy in lung cancer treatment were summarized and discussed.

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“…MAGE-A1 antigen, glypican-3 (GPC3), FRβ, CD44v6, CD133, c-MET, Olfactory receptor 2H1 (OR2H1), CD47, GD2, CD147, prostate stem cell antigen (PSCA), Fibroblast activating protein (FAP), EphA2 and PTK7 are also expected to be targets of CAR in the context of LCa, with preclinical studies completed [190,195,203,204,[208][209][210][211][212][213][214][215][216][217][218] (Fig. 3).…”

Section: Lung Cancer (Lca)mentioning

confidence: 99%

Tumor buster - where will the CAR-T cell therapy ‘missile’ go?

Zhang

Cao

et al. 2022

Mol Cancer

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Chimeric antigen receptor (CAR) T cell (CAR-T cell) therapy based on gene editing technology represents a significant breakthrough in personalized immunotherapy for human cancer. This strategy uses genetic modification to enable T cells to target tumor-specific antigens, attack specific cancer cells, and bypass tumor cell apoptosis avoidance mechanisms to some extent. This method has been extensively used to treat hematologic diseases, but the therapeutic effect in solid tumors is not ideal. Tumor antigen escape, treatment-related toxicity, and the immunosuppressive tumor microenvironment (TME) limit their use of it. Target selection is the most critical aspect in determining the prognosis of patients receiving this treatment. This review provides a comprehensive summary of all therapeutic targets used in the clinic or shown promising potential. We summarize CAR-T cell therapies’ clinical trials, applications, research frontiers, and limitations in treating different cancers. We also explore coping strategies when encountering sub-optimal tumor-associated antigens (TAA) or TAA loss. Moreover, the importance of CAR-T cell therapy in cancer immunotherapy is emphasized.

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Enhanced AC133-specific CAR T cell therapy induces durable remissions in mice with metastatic small cell lung cancer

Cited by 20 publications

References 40 publications

IL-18–secreting CAR T cells targeting DLL3 are highly effective in small cell lung cancer models

IL-18–secreting CAR T cells targeting DLL3 are highly effective in small cell lung cancer models

Research progress of biomarkers in the prediction of anti-PD-1/PD-L1 immunotherapeutic efficiency in lung cancer

Tumor buster - where will the CAR-T cell therapy ‘missile’ go?

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