Journal of immunotherapy
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Journal of immunotherapy · Sep 2006
Dendritic cells loaded with killed allogeneic melanoma cells can induce objective clinical responses and MART-1 specific CD8+ T-cell immunity.
Dendritic cells (DCs) loaded with killed allogeneic tumors can cross-prime tumor-specific naive CD8 T cells in vitro, thereby providing an option to overcome human leukocyte antigen restriction inherent to loading DC vaccines with peptides. We have vaccinated 20 patients with stage IV melanoma with autologous monocyte-derived DCs loaded with killed allogeneic Colo829 melanoma cell line. DCs were generated by culturing monocytes with granulocyte macrophage-colony stimulating factor (granulocyte macrophage-colony stimulating factor) and interleukin (IL-4) and activated by additional culture with tumor necrosis factor and CD40 ligand. ⋯ Two of 3 patients showed improved immune function after vaccinations demonstrated by improved secretion of interferon (IFN)-gamma or T-cell proliferation in response to MART-1 derived peptides. In one of these patients, vaccination led to elicitation of CD8 T-cell immunity specific to a novel peptide-derived from MART-1 antigen, suggesting that cross-priming/presentation of melanoma antigens by DC vaccine had occurred. Thus, the present results justify the design of larger follow-up studies to assess the clinical response to DC vaccines loaded with killed allogeneic tumor cells in patients with metastatic melanoma.
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Journal of immunotherapy · Jul 2003
Randomized Controlled Trial Clinical TrialInterferon-gamma or granulocyte-macrophage colony-stimulating factor administered as adjuvants with a vaccine of irradiated autologous tumor cells from short-term cell line cultures: a randomized phase 2 trial of the cancer biotherapy research group.
The objective was to study the effects of patient-specific vaccine immunotherapy administered with either interferon-gamma (IFNgamma) or granulocyte-macrophage colony stimulating factor (GM-CSF) in patients with metastatic cancer. Short-term cell lines were established from cancer tissue resected from patients with metastatic cancer for use as autologous tumor cell vaccines. Successful cultures were expanded to 1 to 2 x 108 cells, irradiated, and cryopreserved in aliquots of 106 cells for intradermal testing of delayed tumor hypersensitivity and 107 cells for subcutaneous vaccinations. ⋯ Both adjuvants were well tolerated and results were similar in both arms of the study. Both adjuvants were associated with a 25% to 30% rate of DTH conversion and a 25% 5-year survival rate. Immune recognition of autologous tumor can be induced with this approach.
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Journal of immunotherapy · May 2001
ReviewMHC class II-restricted tumor antigens recognized by CD4+ T cells: new strategies for cancer vaccine design.
The adoptive transfer of tumor-infiltrating lymphocytes (TIL) can mediate tumor regression in patients with melanoma. This finding has led to the identification and characterization of tumor-associated antigens recognized by CD8+ TIL. Several clinical trials based on the genes recognized by these CD8+ T cells have been attempted, but with only limited success. ⋯ In this report, we review emerging molecular approaches in cloning major histocompatibility complex (MHC) class II restricted tumor antigens recognized by CD4+ T cells as well as approaches to identify new MHC class II-restricted epitopes from known tumor antigens recognized by CD8+ cytotoxic T lymphocytes and/or antibodies. Progress made in this field has shed light on the roles of tumor antigen-specific CD4+ T cells in humans; it has also provided new insights into the understanding of tumor genesis and the interaction between tumor and the immune system. More importantly, the discovery of MHC class II-restricted tumor antigens has provided opportunities for developing a new generation of cancer vaccines aimed at eliciting both CD4+ and CD8+ T-cell responses against tumor.
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Journal of immunotherapy · May 2001
Tumor cell expression of CD59 is associated with resistance to CD20 serotherapy in patients with B-cell malignancies.
The anti-CD20 chimeric monoclonal antibody rituximab (Rituxan) is used to treat patients with various B-cell tumors, including patients with plasma cell dyscrasias who have CD20+ disease. Many patients with CD20+ disease have either primary unresponsive disease or progress after initially responding to rituximab; therefore, understanding how tumor cells are, or become, resistant to rituximab is of clinical relevance. In this report, we determined whether tumor cells express antigens that block complement-mediated lysis or antibody-dependent cell-mediated cytotoxicity (ADCC) and thereby contribute to rituximab resistance. ⋯ FasL, MUC1, and/or TRAIL were coexpressed with complement regulators on many of these cells. These studies therefore show that complement regulators, particularly CD59 and antigens that may block ADCC, are present on various B-cell tumors and associated with rituximab resistance in patients. A prospective, clinical study is assessing the role of these antigens in mediating rituximab resistance.
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Journal of immunotherapy · May 2001
CD20-directed antibody-mediated immunotherapy induces responses and facilitates hematologic recovery in patients with Waldenstrom's macroglobulinemia.
Waldenstrom's macroglobulinemia (WM, lymphoplasmacytic lymphoma) is a B-cell lymphoproliferative disorder in which CD20 is expressed on tumor cells from most patients. Several small studies have suggested a benefit from the anti-CD20 monoclonal antibody rituximab (Rituxan, MabThera) in patients with WM. In this retrospective study, we examined the outcome of 30 previously unreported patients with WM who received treatment with single-agent rituximab (median age 60; range 32-83 years old). ⋯ These studies therefore demonstrate that rituximab is an active agent in WM. Marked increases in HCT and PLT counts were noted for most patients, including patients with WM who had MR or SD. A prospective clinical trial to more completely define the benefit of single-agent rituximab in patients with WM has been initiated by many of our centers.