This application is a synthesis of didactic training in clinical research, translational immunology and clinical protocol development. Its focus is the study of cytokine-induced modulation of innate immunity in combination with monoclonal antibody (mAb) therapy as a novel immunotherapeutic approach in lymphoma. Its goals are to discover the role played by specific innate immune effector cell subsets in the anti-lymphoma activity of mAbs in vivo and to learn how in vivo modulation of effector cell subsets with cytokines, such as interleukin-2 (IL-2), might enhance the clinical effectiveness of mAbs. The applicant is an Assistant Professor of Internal Medicine at The Ohio State University (OSU) with extensive training in basic cancer laboratory research, cytokine biology, and medical oncology, with a strong concentration in lymphoma. For his academic career development, the applicant has chosen the arena of clinical research in hematological malignancies, with a specific focus in lymphoma. OSU has assembled a cadre of outstanding investigators with expertise in clinical cancer research, particularly in the area of hematological malignancies, providing an excellent environment for career development. The mentor for this application is a recognized leader in the study of the immune system and its role in the pathogenesis and therapy of lymphoma, and has an extensive track record of training successful physician-scientists. This proposal presents two specific aims:
Specific Aim 1 : To participate in a NIH K30- funded Clinical Research Curriculum (CRC) specifically designed for the development of clinical investigators at OSU.
Specific Aim 2 : Based on extensive pre-clinical observations made in the mentor's laboratory, the applicant will complete a Phase I and initiate a Phase II study of rituximab (anti-CD20 monoclonal antibody) and interleukin-2 (IL-2) in relapsed B-cell lymphoma. Correlative science studies in Specific Aim 2 will focus on the study of NK-cells, Fcgamma receptors, ADCC, and pharmacokinetics, with the goal of elucidating the interactions between the innate immune system and rituximab that are relevant to the clinical anti-lymphoma activity of rituximab. These studies will advance our knowledge about the role of the innate immune system in the therapy of lymphoma and may lead to a broader use of cytokine-mAb combinations in the therapy of cancer.
| Khan, Khuda D; Emmanouilides, Christos; Benson Jr, Don M et al. (2006) A phase 2 study of rituximab in combination with recombinant interleukin-2 for rituximab-refractory indolent non-Hodgkin's lymphoma. Clin Cancer Res 12:7046-53 |
| Eisenbeis, Charles F; Grainger, Andrew; Fischer, Beth et al. (2004) Combination immunotherapy of B-cell non-Hodgkin's lymphoma with rituximab and interleukin-2: a preclinical and phase I study. Clin Cancer Res 10:6101-10 |
| Larson, R A; Daley, G Q; Schiffer, C A et al. (2003) Treatment by design in leukemia, a meeting report, Philadelphia, Pennsylvania, December 2002. Leukemia 17:2358-82 |
