The Experts below are selected from a list of 17484 Experts worldwide ranked by ideXlab platform
Lih Hwa Hwang - One of the best experts on this subject based on the ideXlab platform.
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Tumor induced immunosuppression a barrier to immunotherapy of large Tumors by cytokine secreting Tumor Vaccine
Human Gene Therapy, 2000Co-Authors: Chia Ling Hsieh, Dingshinn Chen, Lih Hwa HwangAbstract:An active immunotherapy strategy with cytokine-assisted Tumor Vaccine, although often effective for small Tumor burdens, is much less so for large Tumor burdens. This study examines how large Tumors might suppress the T cell functions and escape from the immune responses elicited by a granulocyte-macrophage colonystimulating factor (GM-CSF)-secreting Tumor Vaccine. According to our results, the T cells isolated from the Tumor-bearing mice treated late with the Vaccine failed to confer protective activity on naive mice against a wild-type Tumor challenge, unlike those isolated from the early-treated group. Nevertheless, the antiTumor activity of the inactive T cells could be restored on in vitro stimulation. Expression of transforming growth factor beta (TGF-beta) and interleukin 10 (IL-10), the potent immunosuppressive factors, was detected in the parental Tumor cell line RL? 1 (a murine T leukemia cell line), as well as in the Tumor region, the levels of which correlated with Tumor progression. An in vit...
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Regression of orthotopic brain Tumors by cytokine-assisted Tumor Vaccines primed in the brain.
Cancer gene therapy, 1999Co-Authors: Sheng-hong Tseng, Chia Ling Hsieh, Swei Ming Lin, Lih Hwa HwangAbstract:This study investigated the therapeutic effects of a rat glioma cell line, C6, that was engineered to secrete mouse GM-CSF (mGM-CSF) on intracerebral (i.c.) brain Tumors. Significant antiTumor immunity was induced in rats when the live or irradiated mGM-CSF-secreting Tumor Vaccine was implanted i.c. The antiTumor activity was effective on small Tumors and, to a lesser extent, on large Tumors or Tumors existing in vivo for a longer duration. Immunohistochemical analysis revealed cellular infiltrates (granulocytes, macrophages, and CD4+ and CD8+ T cells) at both the Vaccine site and the Tumor site, indicating that immune responses were similarly activated when Tumor Vaccine was inoculated in the brain, as at the subcutis. Additional studies demonstrated that the therapeutic effects of Tumor Vaccines on the large Tumors or the long-existing Tumors were enhanced by strategies such as increasing the dosage of Tumor Vaccines, using combined Vaccines consisting of mGM-CSF and human interleukin-2, or combining Tumor Vaccine with herpes simplex virus thymidine kinase/ganciclovir treatment. All of the modified strategies yielded synergistic therapeutic effects on the large Tumor burdens. The data presented herein suggest that cytokine gene therapy is highly promising for the treatment of i.c. gliomas.
Silvia Petrik - One of the best experts on this subject based on the ideXlab platform.
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a feasibility study of cyclophosphamide trastuzumab and an allogeneic gm csf secreting breast Tumor Vaccine for her2 metastatic breast cancer
Cancer immunology research, 2014Co-Authors: Gang Chen, Justin M Asquith, James M Leatherman, Silvia Petrik, Marina Laiko, Maithili M Daphtary, Richa Gupta, Elizabeth Garrettmayer, Nancy E Davidson, Kellie HirtAbstract:Granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting Tumor Vaccines are bioactive, but limited by disease burden and immune tolerance. Cyclophosphamide augments Vaccine activity in tolerant neu mice and in patients with metastatic breast cancer. HER2-specific monoclonal antibodies (mAb) enhance Vaccine activity in neu mice. We hypothesized that cyclophosphamide-modulated vaccination with HER2-specific mAb safely induces relevant HER2-specific immunity in neu mice and patients with HER2+ metastatic breast cancer. Adding both cyclophosphamide and the HER2-specific mAb 7.16.4 to vaccination maximized HER2-specific CD8+ T-cell immunity and Tumor-free survival in neu transgenic mice. We, therefore, conducted a single-arm feasibility study of cyclophosphamide, an allogeneic HER2+ GM-CSF-secreting breast Tumor Vaccine, and weekly trastuzumab in 20 patients with HER2+ metastatic breast cancer. Primary clinical trial objectives were safety and clinical benefit, in which clinical benefit represents complete response + partial response + stable disease. Secondary study objectives were to assess HER2-specific T-cell responses by delayed type hypersensitivity (DTH) and intracellular cytokine staining. Patients received three monthly vaccinations, with a boost 6 to 8 months from trial entry. This combination immunotherapy was safe, with clinical benefit rates at 6 months and 1 year of 55% [95% confidence interval (CI), 32%-77%; P = 0.013] and 40% (95% CI, 19%-64%), respectively. Median progression-free survival and overall survival durations were 7 months (95% CI, 4-16) and 42 months (95% CI, 22-70), respectively. Increased HER2-specific DTH developed in 7 of 20 patients [of whom 4 had clinical benefit (95% CI, 18-90)], with a trend toward longer progression-free survival and overall survival in DTH responders. Polyfunctional HER2-specific CD8+ T cells progressively expanded across vaccination cycles. Further investigation of cyclophosphamide-modulated vaccination with trastuzumab is warranted.
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timed sequential treatment with cyclophosphamide doxorubicin and an allogeneic granulocyte macrophage colony stimulating factor secreting breast Tumor Vaccine a chemotherapy dose ranging factorial study of safety and immune activation
Journal of Clinical Oncology, 2009Co-Authors: Leisha A Emens, Barbara A Biedrzycki, Justin M Asquith, James M Leatherman, Barry Kobrin, Silvia Petrik, Marina Laiko, Joy Levi, Maithili M Daphtary, Antonio C WolffAbstract:Purpose Granulocyte-macrophage colony-stimulating factor (GM-CSF) –secreting Tumor Vaccines have demonstrated bioactivity but may be limited by disease burdens and immune tolerance. We tested the hypothesis that cyclophosphamide (CY) and doxorubicin (DOX) can enhance Vaccine-induced immunity in patients with breast cancer. Patients and Methods We conducted a 3 × 3 factorial (response surface) dose-ranging study of CY, DOX, and an HER2-positive, allogeneic, GM-CSF–secreting Tumor Vaccine in 28 patients with metastatic breast cancer. Patients received three monthly immunizations, with a boost 6 to 8 months from study entry. Primary objectives included safety and determination of the chemotherapy doses that maximize HER2-specific immunity. Results Twenty-eight patients received at least one immunization, and 16 patients received four immunizations. No dose-limiting toxicities were observed. HER2-specific delayed-type hypersensitivity developed in most patients who received Vaccine alone or with 200 mg/m2 CY....
Maithili M Daphtary - One of the best experts on this subject based on the ideXlab platform.
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a feasibility study of cyclophosphamide trastuzumab and an allogeneic gm csf secreting breast Tumor Vaccine for her2 metastatic breast cancer
Cancer immunology research, 2014Co-Authors: Gang Chen, Justin M Asquith, James M Leatherman, Silvia Petrik, Marina Laiko, Maithili M Daphtary, Richa Gupta, Elizabeth Garrettmayer, Nancy E Davidson, Kellie HirtAbstract:Granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting Tumor Vaccines are bioactive, but limited by disease burden and immune tolerance. Cyclophosphamide augments Vaccine activity in tolerant neu mice and in patients with metastatic breast cancer. HER2-specific monoclonal antibodies (mAb) enhance Vaccine activity in neu mice. We hypothesized that cyclophosphamide-modulated vaccination with HER2-specific mAb safely induces relevant HER2-specific immunity in neu mice and patients with HER2+ metastatic breast cancer. Adding both cyclophosphamide and the HER2-specific mAb 7.16.4 to vaccination maximized HER2-specific CD8+ T-cell immunity and Tumor-free survival in neu transgenic mice. We, therefore, conducted a single-arm feasibility study of cyclophosphamide, an allogeneic HER2+ GM-CSF-secreting breast Tumor Vaccine, and weekly trastuzumab in 20 patients with HER2+ metastatic breast cancer. Primary clinical trial objectives were safety and clinical benefit, in which clinical benefit represents complete response + partial response + stable disease. Secondary study objectives were to assess HER2-specific T-cell responses by delayed type hypersensitivity (DTH) and intracellular cytokine staining. Patients received three monthly vaccinations, with a boost 6 to 8 months from trial entry. This combination immunotherapy was safe, with clinical benefit rates at 6 months and 1 year of 55% [95% confidence interval (CI), 32%-77%; P = 0.013] and 40% (95% CI, 19%-64%), respectively. Median progression-free survival and overall survival durations were 7 months (95% CI, 4-16) and 42 months (95% CI, 22-70), respectively. Increased HER2-specific DTH developed in 7 of 20 patients [of whom 4 had clinical benefit (95% CI, 18-90)], with a trend toward longer progression-free survival and overall survival in DTH responders. Polyfunctional HER2-specific CD8+ T cells progressively expanded across vaccination cycles. Further investigation of cyclophosphamide-modulated vaccination with trastuzumab is warranted.
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timed sequential treatment with cyclophosphamide doxorubicin and an allogeneic granulocyte macrophage colony stimulating factor secreting breast Tumor Vaccine a chemotherapy dose ranging factorial study of safety and immune activation
Journal of Clinical Oncology, 2009Co-Authors: Leisha A Emens, Barbara A Biedrzycki, Justin M Asquith, James M Leatherman, Barry Kobrin, Silvia Petrik, Marina Laiko, Joy Levi, Maithili M Daphtary, Antonio C WolffAbstract:Purpose Granulocyte-macrophage colony-stimulating factor (GM-CSF) –secreting Tumor Vaccines have demonstrated bioactivity but may be limited by disease burdens and immune tolerance. We tested the hypothesis that cyclophosphamide (CY) and doxorubicin (DOX) can enhance Vaccine-induced immunity in patients with breast cancer. Patients and Methods We conducted a 3 × 3 factorial (response surface) dose-ranging study of CY, DOX, and an HER2-positive, allogeneic, GM-CSF–secreting Tumor Vaccine in 28 patients with metastatic breast cancer. Patients received three monthly immunizations, with a boost 6 to 8 months from study entry. Primary objectives included safety and determination of the chemotherapy doses that maximize HER2-specific immunity. Results Twenty-eight patients received at least one immunization, and 16 patients received four immunizations. No dose-limiting toxicities were observed. HER2-specific delayed-type hypersensitivity developed in most patients who received Vaccine alone or with 200 mg/m2 CY....
Justin M Asquith - One of the best experts on this subject based on the ideXlab platform.
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a feasibility study of cyclophosphamide trastuzumab and an allogeneic gm csf secreting breast Tumor Vaccine for her2 metastatic breast cancer
Cancer immunology research, 2014Co-Authors: Gang Chen, Justin M Asquith, James M Leatherman, Silvia Petrik, Marina Laiko, Maithili M Daphtary, Richa Gupta, Elizabeth Garrettmayer, Nancy E Davidson, Kellie HirtAbstract:Granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting Tumor Vaccines are bioactive, but limited by disease burden and immune tolerance. Cyclophosphamide augments Vaccine activity in tolerant neu mice and in patients with metastatic breast cancer. HER2-specific monoclonal antibodies (mAb) enhance Vaccine activity in neu mice. We hypothesized that cyclophosphamide-modulated vaccination with HER2-specific mAb safely induces relevant HER2-specific immunity in neu mice and patients with HER2+ metastatic breast cancer. Adding both cyclophosphamide and the HER2-specific mAb 7.16.4 to vaccination maximized HER2-specific CD8+ T-cell immunity and Tumor-free survival in neu transgenic mice. We, therefore, conducted a single-arm feasibility study of cyclophosphamide, an allogeneic HER2+ GM-CSF-secreting breast Tumor Vaccine, and weekly trastuzumab in 20 patients with HER2+ metastatic breast cancer. Primary clinical trial objectives were safety and clinical benefit, in which clinical benefit represents complete response + partial response + stable disease. Secondary study objectives were to assess HER2-specific T-cell responses by delayed type hypersensitivity (DTH) and intracellular cytokine staining. Patients received three monthly vaccinations, with a boost 6 to 8 months from trial entry. This combination immunotherapy was safe, with clinical benefit rates at 6 months and 1 year of 55% [95% confidence interval (CI), 32%-77%; P = 0.013] and 40% (95% CI, 19%-64%), respectively. Median progression-free survival and overall survival durations were 7 months (95% CI, 4-16) and 42 months (95% CI, 22-70), respectively. Increased HER2-specific DTH developed in 7 of 20 patients [of whom 4 had clinical benefit (95% CI, 18-90)], with a trend toward longer progression-free survival and overall survival in DTH responders. Polyfunctional HER2-specific CD8+ T cells progressively expanded across vaccination cycles. Further investigation of cyclophosphamide-modulated vaccination with trastuzumab is warranted.
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timed sequential treatment with cyclophosphamide doxorubicin and an allogeneic granulocyte macrophage colony stimulating factor secreting breast Tumor Vaccine a chemotherapy dose ranging factorial study of safety and immune activation
Journal of Clinical Oncology, 2009Co-Authors: Leisha A Emens, Barbara A Biedrzycki, Justin M Asquith, James M Leatherman, Barry Kobrin, Silvia Petrik, Marina Laiko, Joy Levi, Maithili M Daphtary, Antonio C WolffAbstract:Purpose Granulocyte-macrophage colony-stimulating factor (GM-CSF) –secreting Tumor Vaccines have demonstrated bioactivity but may be limited by disease burdens and immune tolerance. We tested the hypothesis that cyclophosphamide (CY) and doxorubicin (DOX) can enhance Vaccine-induced immunity in patients with breast cancer. Patients and Methods We conducted a 3 × 3 factorial (response surface) dose-ranging study of CY, DOX, and an HER2-positive, allogeneic, GM-CSF–secreting Tumor Vaccine in 28 patients with metastatic breast cancer. Patients received three monthly immunizations, with a boost 6 to 8 months from study entry. Primary objectives included safety and determination of the chemotherapy doses that maximize HER2-specific immunity. Results Twenty-eight patients received at least one immunization, and 16 patients received four immunizations. No dose-limiting toxicities were observed. HER2-specific delayed-type hypersensitivity developed in most patients who received Vaccine alone or with 200 mg/m2 CY....
James M Leatherman - One of the best experts on this subject based on the ideXlab platform.
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a feasibility study of cyclophosphamide trastuzumab and an allogeneic gm csf secreting breast Tumor Vaccine for her2 metastatic breast cancer
Cancer immunology research, 2014Co-Authors: Gang Chen, Justin M Asquith, James M Leatherman, Silvia Petrik, Marina Laiko, Maithili M Daphtary, Richa Gupta, Elizabeth Garrettmayer, Nancy E Davidson, Kellie HirtAbstract:Granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting Tumor Vaccines are bioactive, but limited by disease burden and immune tolerance. Cyclophosphamide augments Vaccine activity in tolerant neu mice and in patients with metastatic breast cancer. HER2-specific monoclonal antibodies (mAb) enhance Vaccine activity in neu mice. We hypothesized that cyclophosphamide-modulated vaccination with HER2-specific mAb safely induces relevant HER2-specific immunity in neu mice and patients with HER2+ metastatic breast cancer. Adding both cyclophosphamide and the HER2-specific mAb 7.16.4 to vaccination maximized HER2-specific CD8+ T-cell immunity and Tumor-free survival in neu transgenic mice. We, therefore, conducted a single-arm feasibility study of cyclophosphamide, an allogeneic HER2+ GM-CSF-secreting breast Tumor Vaccine, and weekly trastuzumab in 20 patients with HER2+ metastatic breast cancer. Primary clinical trial objectives were safety and clinical benefit, in which clinical benefit represents complete response + partial response + stable disease. Secondary study objectives were to assess HER2-specific T-cell responses by delayed type hypersensitivity (DTH) and intracellular cytokine staining. Patients received three monthly vaccinations, with a boost 6 to 8 months from trial entry. This combination immunotherapy was safe, with clinical benefit rates at 6 months and 1 year of 55% [95% confidence interval (CI), 32%-77%; P = 0.013] and 40% (95% CI, 19%-64%), respectively. Median progression-free survival and overall survival durations were 7 months (95% CI, 4-16) and 42 months (95% CI, 22-70), respectively. Increased HER2-specific DTH developed in 7 of 20 patients [of whom 4 had clinical benefit (95% CI, 18-90)], with a trend toward longer progression-free survival and overall survival in DTH responders. Polyfunctional HER2-specific CD8+ T cells progressively expanded across vaccination cycles. Further investigation of cyclophosphamide-modulated vaccination with trastuzumab is warranted.
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timed sequential treatment with cyclophosphamide doxorubicin and an allogeneic granulocyte macrophage colony stimulating factor secreting breast Tumor Vaccine a chemotherapy dose ranging factorial study of safety and immune activation
Journal of Clinical Oncology, 2009Co-Authors: Leisha A Emens, Barbara A Biedrzycki, Justin M Asquith, James M Leatherman, Barry Kobrin, Silvia Petrik, Marina Laiko, Joy Levi, Maithili M Daphtary, Antonio C WolffAbstract:Purpose Granulocyte-macrophage colony-stimulating factor (GM-CSF) –secreting Tumor Vaccines have demonstrated bioactivity but may be limited by disease burdens and immune tolerance. We tested the hypothesis that cyclophosphamide (CY) and doxorubicin (DOX) can enhance Vaccine-induced immunity in patients with breast cancer. Patients and Methods We conducted a 3 × 3 factorial (response surface) dose-ranging study of CY, DOX, and an HER2-positive, allogeneic, GM-CSF–secreting Tumor Vaccine in 28 patients with metastatic breast cancer. Patients received three monthly immunizations, with a boost 6 to 8 months from study entry. Primary objectives included safety and determination of the chemotherapy doses that maximize HER2-specific immunity. Results Twenty-eight patients received at least one immunization, and 16 patients received four immunizations. No dose-limiting toxicities were observed. HER2-specific delayed-type hypersensitivity developed in most patients who received Vaccine alone or with 200 mg/m2 CY....
