The proposed career development training plan will provide the candidate, Dr. Amod Sarnaik, with a pathway to independence as a researcher. Dr. Sarnaik's long term career goal is to become an established translational scientist with expertise in surgically-oriented immune-based early phase clinical trials. Dr. Sarnaik's immediate goal is to acquire specific skills in clinical and translational laboratory research, biostatistics, and grnt writing. The training plan includes didactic and practical experiences in each of these elements and is designed to capitalize on existing resources at Moffitt Cancer Center as well as the specific expertise of the mentors included in the training plan. The proposed research plan is a logical extension of Dr. Sarnaik's preliminary data. This includes implementation of a phase I clinical trial that combines co- stimulatory antibodies and adoptive cell therapy with tumor-infiltrating lymphocytes (TIL) for patients with stage IV melanoma that are unresectable for curative intent. Adoptive cell therapy is a recent innovation in immunotherapy for metastatic melanoma, and combination with co-stimulatory antibodies has the potential to improve patient outcomes. This trial will determine the safety and feasibility of this combination treatment. Additionally, the mechanisms by which co-stimulation enhances outcomes will be determined by investigating known factors important for T cell-mediated anti-tumor responses. Results will directly lead to the development of a phase II trial. The career development training plan will involve close mentoring by Dr. Jeffrey Weber, as well as oversight by an advisory committee. The co-mentors of the grant will provide additional training in phase I clinical trial design and analysis, translational laboratory research, clinical trial development, and biostatistics. Key elements of the career development plan include: weekly interactions with Dr. Weber, rotations in Clinical Pharmacology, the Clinical Research Unit (Phase I/II trial monitoring and care), and the laboratory of Dr. James Mul?. In addition, training in biostatistics by Dr. Ji-Hyun Lee and training in grant writing will be obtained. It is anticipated that these experiences will lead to a R01 submission by the end of the term of the grant. Moffitt Cancer Center provides an ideal and unique training environment for this opportunity. The training proposed in this K23 training grant will allow Dr. Sarnaik to transition to an independent translational and clinical trial researcher.
For the research plan of this K23 proposal, I propose a phase I clinical trial combining co-stimulatory antibodies and adoptive cell therapy with tumor-infiltratin lymphocytes (TIL) for patients with stage IV melanoma that are unresectable for cure. Patient- derived specimens from this trial will be used to determine the mechanisms by which the co-stimulatory antibodies enhance adoptive cell therapy. The long term goal of this project is to apply our expanding knowledge of T cell biology to improve the promising, emerging treatment of adoptive cell therapy for metastatic melanoma.
|Hall, MacLean; Liu, Hao; Malafa, Mokenge et al. (2016) Expansion of tumor-infiltrating lymphocytes (TIL) from human pancreatic tumors. J Immunother Cancer 4:61|
|Kodumudi, Krithika N; Siegel, Jessica; Weber, Amy M et al. (2016) Immune Checkpoint Blockade to Improve Tumor Infiltrating Lymphocytes for Adoptive Cell Therapy. PLoS One 11:e0153053|
|Doepker, Matthew P; Thompson, Zachary J; Harb, Jennifer N et al. (2016) Dermal melanoma: A report on prognosis, outcomes, and the utility of sentinel lymph node biopsy. J Surg Oncol 113:98-102|
|Doepker, Matthew P; Thompson, Zachary J; Fisher, Kate J et al. (2016) Is a Wider Margin (2Â cm vs. 1Â cm) for a 1.01-2.0Â mm Melanoma Necessary? Ann Surg Oncol 23:2336-42|
|Sung, Hyeran; Kanchi, Krishna L; Wang, Xue et al. (2016) Inactivation of RASA1 promotes melanoma tumorigenesis via R-Ras activation. Oncotarget 7:23885-96|
|Liu, Hao; Innamarato, Pasquale Patrick; Kodumudi, Krithika et al. (2016) Intralesional rose bengal in melanoma elicits tumor immunity via activation of dendritic cells by the release of high mobility group box 1. Oncotarget 7:37893-37905|
|Dossett, Lesly A; Castner, Nicholas B; Pow-Sang, Julio M et al. (2016) Robotic-Assisted Transperitoneal Pelvic Lymphadenectomy for Metastatic Melanoma: Early Outcomes Compared with Open Pelvic Lymphadenectomy. J Am Coll Surg 222:702-9|
|Jakub, James W; Terando, Alicia M; Sarnaik, Amod et al. (2016) Safety and Feasibility of Minimally Invasive Inguinal Lymph Node Dissection in Patients With Melanoma (SAFE-MILND): Report of a Prospective Multi-institutional Trial. Ann Surg :|
|Sloot, Sarah; Rashid, Omar M; Sarnaik, Arnod A et al. (2016) Developments in Intralesional Therapy for Metastatic Melanoma. Cancer Control 23:12-20|
|Lienlaf, M; Perez-Villarroel, P; Knox, T et al. (2016) Essential role of HDAC6 in the regulation of PD-L1 inÂ melanoma. Mol Oncol 10:735-50|
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