Kwon, Eugene D.Overview
Publication Timeline
Most widely held works by
Eugene D Kwon
A Phase II Immunotherapeutic Trial: Combination Androgen Ablative Therapy and CTLA-4 Blockade as a Treatment for Advanced Prostate Cancer
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Book
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3 editions published between 2003 and 2006 in English and held by 1 library worldwide This is an open-label, two-center, randomized phase II trial in which 108 patients with newly diagnosed advanced prostate cancer will be prospectively enrolled onto study. Patients with T3, NO, MX prostate cancer or patients with any T stage, Ni (defined as a single positive lymph node 2cm or less in size) and/or limited skeletal metastases will be considered for study inclusion. Limited skeletal metastases is defined as <3 metastatic lesions on bone scan. Patients must have undergone diagnosis and staging of their prostate cancer within 120 days of enrollment. Upon enrollment patients will be immediately randomized to receive either: i) 3 months of concurrent AA therapy + MDX-OlO (treatment group) or ii) 3 months of initial AA therapy alone (control group). Fifty four patients will be randomized at the Mayo Clinic, while the remaining 54 patients will be randomized at the University of California-San Francisco Comprehensive Cancer Center. Equal numbers of control and treatment group patients will be enrolled onto study at these two institutions over a period of eighteen months.
A Phase II Immunotherapeutic Trial: Combination Androgen Ablative Therapy Treatment for Advanced Prostate Cancer
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Book
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2 editions published between 2008 and 2009 in English and held by 1 library worldwide The objectives of this study are to test whether CTLA 4 blockade + AA therapy canenhance clinical treatment responses in advanced prostate cancer patients relative to AA therapy alone. Study patients are randomized to 3 months of combined AA therapy + MDX-010 or versus AA therapy alone. To date, 46 patients have been enrolled and 42 randomized per protocol. An additional 84 patients have been screened and deemed ineligible for study. 29 patients now have sufficient follow-up to assess if any treatment effects may be occurring. In general, patients receiving combined AA + MDX-010 have exhibited greater PSA responses than patients receiving AA therapy alone. We have also observed that MDX-010 does not likely affect initial testosterone production but may delay testosterone recovery. Our preliminary studies also indicate atypical and favorable responses to combined MDX-010 + AA therapy including reversal of rising PSA, rapid resolution of obstructive urinary pathology and dramatic tumor downstaging resulting in unexpected 1 year disease-free patient status. Based on these preliminary observations, we believe that combined AA + MDX-010 treatment may encompass a promising approach to improve advanced prostate cancer treatment.
Lowering T Cell Activation Thresholds and Deregulating Homeostasis to Facilitate Immunotherapeutic Responses to Treat Prostate Cancer
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Book
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2 editions published between 2005 and 2006 in English and held by 1 library worldwide The inductor of tumor-specific T cells remains a primary obstacle to immunotherapeutic approaches for most cancers including prostate cancer This difficulty has been largely ascribed to mechanisms for tumor evasion of the immune system and host-imposed restrictions (collectively referred to as tolerance) that prevent cross-reactive autoimmunity against the parent tissues from which tumors arise. Limitations in techniques to identify novel and truly immunogenic prostate-spew antigens and efficient methods to modify autologous tissues for vaccine preparation have further constrained approaches to develop immune-based therapies for prostate cancer Hence, relatively straightforward manipulations that induce specific T cell responses against prostate tumors or epithelial tissues, especially in vivo, might ultimately prove valuable for prostate cancer immunotherapy Our studies explore a new paradigm in which we will exploit blockade of T cell purigenic receptors A2a and A2b (using caffeine) to alleviate tumor-induced impairments in T cell function to potentiate T cell-mediated immunotherapeutic responses to treat established prostate tumors in mice.
Androgen Ablation Combined With CTLA-4 Blockade-Based Immunotherapy as a Treatment for Prostate Cancer
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Book
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2 editions published between 2001 and 2003 in English and held by 1 library worldwide Manipulations capable of repealing host tolerance to induce T cell-mediated prostate tissue-specific responses are of central importance to immunotherapeutic approaches to prostate cancer treatment. Hence in the current proposal, we test whether androgen ablation (by castration) can induce T cell responses targeting murine prostate epithelial and tumor cells. To date, we have found that castration of TRAMP mice results in prostate and tumor infiltration by antigen presenting cells (APC's) as well as CD4+ and CD8+ T cells. These studies complete our original Specific Aim 1 and suggest that castration can prime host responses amenable to immunotherapeutic potentiation. Further studies proposed in our original Specific Aims 2 and 3 will address the potential of androgen ablation to facilitate/potentiate novel immunotherapies, including manipulations that license APC's or prevent T cell downregulation, for prostate cancer treatment.
Androgen Ablation Combined with CTLA-4 Blockage-Based Immunotherapy as a Treatment for Prostate Cancer
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Book
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1 edition published in 2002 in English and held by 1 library worldwide Manipulations capable of repealing host tolerance to induce T cell-mediated prostate tissue specific responses are of central importance to immunotherapeutic approaches to prostate cancer treatment. Hence in the current proposal, we test whether androgen ablation (by castration) can induce T cell responses targeting murine prostate epithelial and tumor cells. We previously showed that castration of TRAMP mice results in prostate and tumor infiltration by antigen presenting cells (APC's) as well as CD4+ and CD8+ T cells. These studies completed our original Specific Aizn 1 and suggested that castration can prime host responses amenable to immunotherapeutic potentiation. Over the last year we have essentially addressed Specific Aims 2 and 3 by showing that androgen ablation can facilitate/potentiate the effectiveness of novel immunotherapies (anti-CD40 and anti-CTLA- 4 treatment) to enhance T cell-mediated TRAMP tumor inflammation for prostate cancer treatment. Hence, we have extended our studies by conducting a number of exploratory experiments to elucidate central mechanisms whereby androgen ablation augments T cell- mediated immunity.  Related Identities |
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