The goal of this proposal is to provide mentoring for beginning clinical investigators within the framework of the principal I investigator's program of novel immunotherapeutic clinical trials. Some of the most exciting new anti-cancer therapies are based on immunologic discoveries. For example, recombinant cytokines and monoclonal antibodies are now routinely used in the setting of advanced disease, usually in combination with cytotoxic chemotherapy. Unfortunately, these regimens can be toxic, and it is not clear that combining these agents with standard chemotherapeutic drugs represents the most logical approach to their development. An alternate approach that has been employed by Dr. Carson, is the use of cytokine adjuvants to improve the efficacy of immunologic therapies. Dr. Carson's clinical program has focused on two specific areas of investigation: (1) The use of interleukin-12 and other cytokines to enhance the sensitivity of tumors to the actions of interferon-alpha; and (2). The use of cytokines to augment the immune response to an anti-HER2/neu monoclonal antibody. These trials all have evolved from basic experimental observations that were made in Dr. Carson's research laboratory. In order to, evaluate the effects of these treatments on the activity of the patient's immune system and the growth of the patient's tumor, Dr. Carson has conducted a series of novel correlative studies utilizing patient tissues. These laboratory studies have permitted a rational evaluation of the immunotherapeutic regimens and have guided the development of subsequent trials. A number of Medical and Surgical Oncology Fellows at the Ohio State University Comprehensive Cancer Center have I participated in the development and conduct of Dr. Carson's clinical trials. He has been able to train these young investigators I in many aspects of clinical research as they evaluate and treat patients enrolled in his immunotherapeutic studies. In the current proposal, Dr. Carson has outlined a detailed plan of patient-oriented research. He has also developed a systematic training program for young investigators who are involved in these clinical trials so that they will eventually be able to generate and administer protocols of their own design. In addition to their clinical research, trainees will engage in a series of educational experiences and specialized training sessions. Trainees will also attend a series of oncologic didactic sessions and will meet regularly with Dr. Carson to discuss their patients and their educational experiences. The promise of multi-institutional trials through the CALGB cooperative group insures that trainees will gain valuable experience in this aspect of clinical research. I Finally, a special emphasis has been placed on instruction relating to the ethical conduct of patient-oriented research.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Midcareer Investigator Award in Patient-Oriented Research (K24)
Project #
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Study Section
Subcommittee G - Education (NCI)
Program Officer
Gorelic, Lester S
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Ohio State University
Schools of Medicine
United States
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Latchana, Nicholas; DiVincenzo, Mallory J; Regan, Kelly et al. (2018) Alterations in patient plasma microRNA expression profiles following resection of metastatic melanoma. J Surg Oncol 118:501-509
Lai, Xiulan; Stiff, Andrew; Duggan, Megan et al. (2018) Modeling combination therapy for breast cancer with BET and immune checkpoint inhibitors. Proc Natl Acad Sci U S A 115:5534-5539
Latchana, Nicholas; Abrams, Zachary B; Howard, J Harrison et al. (2017) Plasma MicroRNA Levels Following Resection of Metastatic Melanoma. Bioinform Biol Insights 11:1177932217694837
McMichael, Elizabeth L; Jaime-Ramirez, Alena Cristina; Guenterberg, Kristan D et al. (2017) IL-21 Enhances Natural Killer Cell Response to Cetuximab-Coated Pancreatic Tumor Cells. Clin Cancer Res 23:489-502
Suarez-Kelly, Lorena P; Kemper, Gregory M; Duggan, Megan C et al. (2016) The combination of MLN2238 (ixazomib) with interferon-alpha results in enhanced cell death in melanoma. Oncotarget 7:81172-81186
Skinner, Cassandra C; McMichael, Elizabeth L; Jaime-Ramirez, Alena C et al. (2016) Folate-conjugated immunoglobulin targets melanoma tumor cells for NK cell effector functions. Melanoma Res 26:329-37
Stiff, Andrew; Trikha, Prashant; Wesolowski, Robert et al. (2016) Myeloid-Derived Suppressor Cells Express Bruton's Tyrosine Kinase and Can Be Depleted in Tumor-Bearing Hosts by Ibrutinib Treatment. Cancer Res 76:2125-36
Jaime-Ramirez, Alena C; McMichael, Elizabeth; Kondadasula, SriVidya et al. (2016) NK Cell-Mediated Antitumor Effects of a Folate-Conjugated Immunoglobulin Are Enhanced by Cytokines. Cancer Immunol Res 4:323-336
Latchana, Nicholas; Regan, Kelly; Howard, J Harrison et al. (2016) Global microRNA profiling for diagnostic appraisal of melanocytic Spitz tumors. J Surg Res 205:350-358
Martin del Campo, Sara E; Levine, Kala M; Mundy-Bosse, Bethany L et al. (2015) The Raf Kinase Inhibitor Sorafenib Inhibits JAK-STAT Signal Transduction in Human Immune Cells. J Immunol 195:1995-2005

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