Treatment of metastatic melanoma with autologous CD4+ T cells against NY-ESO-1. N Engl J Med

Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
New England Journal of Medicine (Impact Factor: 55.87). 07/2008; 358(25):2698-703. DOI: 10.1056/NEJMoa0800251
Source: PubMed


We developed an in vitro method for isolating and expanding autologous CD4+ T-cell clones with specificity for the melanoma-associated antigen NY-ESO-1. We infused these cells into a patient with refractory metastatic melanoma who had not undergone any previous conditioning or cytokine treatment. We show that the transferred CD4+ T cells mediated a durable clinical remission and led to endogenous responses against melanoma antigens other than NY-ESO-1.

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    • "Castriconi et al. demonstrated that stem like cells were highly susceptible to lysis by both allogeneic and autologous activated NK cells[39].Todaro et al.showed killing of human colon CSCs by γδ T lymphocytes in vitro[40]; Contag et al. described cytokine-induced killer cells which could be used as cellular vehicles to deliver oncolytic virus to lymphoma cancer stem like cells[41]. Dendritic cells as the most powerful antigen presenting cells of the body have also been used in experimental animals and numerous clinical trials for induction of effective antitumor immune responses4243444546. Fields et al. have reported that DCs derived from bone marrow and loaded with tumor lysate could potentially induce CTL and T cell proliferation responses[45]; other investigators also showed that vaccination with autologous DCs generated from peripheral blood monocytes is a safe and promising approach for treatment of metastatic melanoma[44]. "
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    ABSTRACT: Significance: The existence of cancer stem cells (CSCs) in many cancers including melanoma and their resistance to conventional regimens of cancer therapy results in post treatment relapse and metastasis of cancer, so targeting the CSC population is the novel goal of several researches. CSC targeted DC based immunotherapy also seems to be a potentially powerful choice for prevention or treatment of cancers. However there are rare studies concerning the use of DCs for targeting of CSCs.
    Full-text · Article · Jan 2016 · Cancer letters
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    • "This trial was based on preclinical studies showing that this vaccine can induce CD8 and CD4 T cell responses [20]. Besides vaccination strategies, adoptive cell therapy with autologous T cells transduced with a T-cell receptor directed against NY-ESO-1 showed responses in previously treated patients with NY-ESO-1 bearing tumors; 4 out of 6 patients with advanced synovial cell sarcoma and 5 out of 11 patients with metastatic melanoma had an objective response, and this approach is now being studied in additional patients, using NY-ESO-1 tumor expression as a criterion for eligibility [19, 43]. "
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    ABSTRACT: Background: Novel immune therapies targeting tumor specific antigens are being developed. Our purpose was to determine expression of the cancer testes antigen NY-ESO-1 in renal cell carcinoma (RCC), as NY-ESO-1 targeting approaches, particularly adoptive cell therapy, have not been evaluated in this disease. Methods: We employed tissue microarrays containing >300 unique RCC cases and adjacent benign renal tissue to determine NY-ESO-1 expression using a quantitative immunofluorescence method. In addition, we studied NY-ESO-1 expression in 35 matched primary and metastatic RCC specimens to assess concordance between different tumor sites. Results: NY-ESO-1 was highly expressed in a subset of RCCs. Expression in primary RCC specimens was significantly higher than adjacent normal renal tissue (P<0.0001) and higher in clear cell carcinomas than papillary RCC (P<0.0001). Expression levels in metastatic specimens were higher than in matched primary samples (P=0.0018), and the correlation between the two sites was modest (χ2=3.5, p=0.06). Conclusions: Aberrant NY-ESO-1 expression seen in clear cell RCC suggests that NY-ESO-1 targeting approaches should be studied in this disease. Expression is higher in metastatic sites, and discordance between primary and metastatic sites in some patients suggests that patient selection for these therapies should be based on expression in metastatic rather than nephrectomy specimens.
    Full-text · Article · Jun 2014 · Oncotarget
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    • "Several preclinical studies have described antitumor effect of ACT using CD4+ T cell population, and CD4+ T cells have cytolytic activity dependent on class II-restricted recognition of tumors [132–134]. In a recent early-phase dose escalation study of ACT for patient with metastatic melanoma using CD4+ T cell clones, the patients experienced partial responses including a case of a complete durable response [128, 135]. "
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    ABSTRACT: Immunotherapy emerged as a promising therapeutic approach to highly incurable malignant gliomas due to tumor-specific cytotoxicity, minimal side effect, and a durable antitumor effect by memory T cells. But, antitumor activities of endogenously activated T cells induced by immunotherapy such as vaccination are not sufficient to control tumors because tumor-specific antigens may be self-antigens and tumors have immune evasion mechanisms to avoid immune surveillance system of host. Although recent clinical results from vaccine strategy for malignant gliomas are encouraging, these trials have some limitations, particularly their failure to expand tumor antigen-specific T cells reproducibly and effectively. An alternative strategy to overcome these limitations is adoptive T cell transfer therapy, in which tumor-specific T cells are expanded ex vivo rapidly and then transferred to patients. Moreover, enhanced biologic functions of T cells generated by genetic engineering and modified immunosuppressive microenvironment of host by homeostatic T cell expansion and/or elimination of immunosuppressive cells and molecules can induce more potent antitumor T cell responses and make this strategy hold promise in promoting a patient response for malignant glioma treatment. Here we will review the past and current progresses and discuss a new hope in adoptive T cell therapy for malignant gliomas.
    Full-text · Article · Jun 2014 · Research Journal of Immunology
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