Immunotherapy, Immune Reconstitution post blood and marrow transplantation
PhD, Microbiology/Immunology, Wake Forest University, Winston-Salem, NC, 1984
My primary research interests have been focused on immune reconstitution after BMT and the use of immunotherapy to improve transplant outcomes. I have been a principle or co-investigator on several protocols conducted under investigational new drug (IND) approvals. Protocols currently active in the clinic include: 1) Use of cytotoxic T cell lines from transplant donors prepared in the laboratory to recognize common viral pathogens (EBV, CMV, Adenovirus) that cause considerable morbidity and mortality in BMT patients who have not yet recovered a fully functioning immune system. This project was entirely developed in my research laboratory and translated to the clinic through the Lymphocyte Propagation Laboratory (LPL). 2) Two step purification of CD3-reduced/CD56-enriched NK cells to prevent disease relapse in two phase I/II clinical trials for hematological malignancies and for pediatric solid tumors. This project is based in the Cell Processing Laboratory (CPL). 3) Preparation of CD34-enriched products for use in a study of transplantation for high-risk sickle cell anemia patients with haploidentical donors. This project is based in the CPL and I serve or the executive committee for this grant-supported multi-center study. 4) Preparation of CD34-enriched products for use in a multi-center phase III Clinical Trials Network (CTN) study of calcineurin inhibitor-Free interventions for prevention of graft-versus host disease. This project is also based in the CPL and I am a member of the protocol team with oversight over other processing laboratories in the multi-center study.
Trials in preclinical development include: 1) Preparation of a Multiple Myeloma/Dendritic Cell fusion vaccine for CTN protocol CTN1401. This study is awaiting final FDA and IRB approvals. Vaccine is prepared in the LPL, and I serve on the trial protocol development committee. 2) The use of TCRαβ/CD19 reduced products in a two-center study of unrelated and partially matched related donor transplants in hematologic malignancies. This trial is awaiting IDE amendment approval to open and will be based in the CPL. 3) Development of a suicide gene protocol using a lenti-TMP-tk-LNGFR vector to transduce primary T cells to re-induce remission in patients who have relapsed post BMT. This study is pending submission to FDA for IND approval and is being developed in the BMT Research Laboratory. 4) Development of a chimeric antigen receptor transduced T cells using a lenti-CD19-CAR vector for the treatment of B cell malignancies, produced entirely within the CliniMACS Prodigy Device. This project is currently in early phases of obtaining technology transfer agreements, protocol development, and preclinical scale up for IND application. This study will transition from the BMT Research Laboratory to the LPL for preparation of lines to be used clinically.