Novel immunotherapy for adult T-cell leukemia/lymphoma: Targeting aurora kinase A

Casey, Nicholas; Fujiwara, Hiroshi; Ochi, Toshiki; Yasukawa, Masaki

doi:10.1080/2162402x.2016.1239006

Cited by 6 publications

(4 citation statements)

References 10 publications

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“…14 The highest combined response rates were observed for the proto-oncogene Her2/neu, the cell cycle protein aurora kinase A, the cancer/testis antigen NY-ESO-1 and the tumor suppressor p53 (Figure 2D), all of which are currently under investigation in clinical trials. [26][27][28][29] In patients with NSCLC, the frequencies of TA-reactive T cells in the bone marrow were significantly lower (p = .0028; Figure 1B) than those in the corresponding peripheral blood sample from the same patient. As shown in our previous study, the presence of preoperatively detected endogenous TA-reactive T cells in the peripheral blood was associated with improved RFS in 51 patients following curative intent surgery for NSCLC.…”

Section: Discussionmentioning

confidence: 95%

Bone marrow expands the repertoire of functional T cells targeting tumor-associated antigens in patients with resectable non-small-cell lung cancer

et al. 2019

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The efficacy of cancer immunotherapy may be improved by increasing the number of circulating tumor-reactive T cells. The bone marrow is a priming site and reservoir for such T cells. The characteristics of bone marrow-derived tumor-reactive T cells are poorly understood in patients with non-small-cell lung cancer (NSCLC). To compare the responsiveness of tumor antigen-reactive T cells from the bone marrow with matched peripheral blood samples in patients with resectable NSCLC, we used flow cytometry, cytokine capture assays and enzyme-linked immunospot assays to examine the responsiveness of T cells to 14 tumor antigens in matched bone marrow and peripheral blood samples from patients with resectable NSCLC or benign tumors and tumor-free patients. T cells with reactivity to tumor antigens were detected in the bone marrow of 20 of 39 (51%) NSCLC patients. The panel of tumor antigens recognized by bone marrow-derived T cells was distinct from that recognized by peripheral blood-derived T cells in NSCLC patients. Unlike for peripheral blood T cells, the presence of tumor-reactive T cells in the bone marrow did not correlate with recurrence-free survival after curative intent resection of NSCLC. T cells with reactivity to tumor antigens are common in the bone marrow of patients with NSCLC. Tumor-reactive T cells of the bone marrow have the potential to significantly broaden the total repertoire of tumor-reactive T cells in the body. To clarify the role of tumor-reactive T cells of the bone marrow in T cell-based immunotherapy approaches, clinical studies are needed (ClinicalTrials.gov: NCT02515760).

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Section: Discussionmentioning

confidence: 95%

Bone marrow expands the repertoire of functional T cells targeting tumor-associated antigens in patients with resectable non-small-cell lung cancer

et al. 2019

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“…Moreover, AURKA-targeted therapies have been recently developed for adult T-cell leukemia/lymphoma (especially MLN8237, also known as alisertib, 1 selective AURKA inhibitor). [42][43][44][45] Although unknown for its functional role in lymphoma, CDCA3 has been identified as a prognostic biomarker and potential therapeutic target in multiple cancers, such as prostate, lung, bladder, colorectal, and gastric The intersection analysis of significantly altered genes (expression change $ twofold; P , .05) was conducted as described above. (E-F) Heat map and enrichment analysis of cancer.…”

Section: Discussionmentioning

confidence: 99%

Developing new ceramide analogs and identifying novel sphingolipid-controlled genes against a virus-associated lymphoma

Chen

Goyal

Dai

et al. 2020

Blood

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Primary effusion lymphoma (PEL) is an aggressive malignancy with poor prognosis even under chemotherapy, usually infected by Kaposi's sarcoma-associated herpesvirus (KSHV), one of human oncogenic viruses. Currently, there is no specific treatment for PEL, therefore developing new therapies is of high importance. Sphingolipid metabolism plays an important role in determining the fate of tumor cells. Our previous studies have demonstrated that there is a correlation between sphingolipid metabolism and KSHV+ tumor cells survival. To further develop sphingolipid metabolism targeted therapy, after screening a series of newly synthesized ceramide analogs, here, we have identified compounds with effective anti-PEL activity. These compounds induce significant PEL apoptosis, cell cycle arrest, and intracellular ceramide production through regulation of ceramide synthesizing or ceramide metabolizing enzymes, and dramatically suppress tumor progression without visible toxicity in vivo. These new compounds also increase viral lytic gene expression in PEL cells. Our comparative transcriptomic analysis revealed their mechanisms of action for inducing PEL cell death, and identified a subset of novel cellular genes including AURKA and CDCA3, controlled by sphingolipid metabolism, and required for PEL survival with functional validation. These data provide the framework for the development of promising sphingolipid-based therapies against this virus-associated malignancy.

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“…High-avidity TCRs specific for human TERT have been identified in AML, B-cell acute lymphoblastic leukemia (B-ALL), and adult T-cell leukemia (ATL) [4, 21, 22]. Additionally, aurora kinase A (AURKA)-specific TCRs [23, 24], murine double-minute 2 oncoprotein (MDM2)-TCRs [25, 26], and B cell-specific transcription factor BOB1-TCRs have been found in multiple myeloma [27], and hyaluronan-mediated motility receptor (HMMR/Rhamm)-TCRs were identified in acute lymphatic leukemia (ALL) and AML [28] (Table 1).…”

Section: Identification Of Leukemia-specific Tcrsmentioning

confidence: 99%

“…AURKA (207–215) -specific TCR-CD8 + T cells also displayed anti-leukemia efficacy in a xenograft mouse model. Therefore, AURKA-TCR-T cell therapy against leukemia is an alternative approach [23, 24].…”

Section: Tcr-t Cells For Leukemia Immunotherapy In Preclinical Studiesmentioning

confidence: 99%

T cell receptor-engineered T cells for leukemia immunotherapy

Zhang

2019

Cancer Cell Int

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At present, refractory and relapse are major issues for leukemia therapy and a major cause of allogeneic hematopoietic stem cell transplant failure. Over the last decade, many studies have demonstrated that adoptive cancer antigen-specific T cell therapy is an effective option for leukemia therapy. Recently, T cell immunotherapy studies have mainly focused on chimeric antigen receptor- and T cell receptor-engineered T cells. Clinical trials involving chimeric antigen receptor-engineered T cells have been a major breakthrough and became a novel therapy for leukemia. As another potential therapy for leukemia, clinical application of TCR-engineered T cells remains in its infancy. This article presents a review of the current status of anti-leukemia immunotherapy using leukemia antigen-specific TCR-engineered T cells.

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Novel immunotherapy for adult T-cell leukemia/lymphoma: Targeting aurora kinase A

Cited by 6 publications

References 10 publications

Bone marrow expands the repertoire of functional T cells targeting tumor-associated antigens in patients with resectable non-small-cell lung cancer

Bone marrow expands the repertoire of functional T cells targeting tumor-associated antigens in patients with resectable non-small-cell lung cancer

Developing new ceramide analogs and identifying novel sphingolipid-controlled genes against a virus-associated lymphoma

T cell receptor-engineered T cells for leukemia immunotherapy

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