Khaled Tolba, M.D.
Assistant Professor of Medical Oncology & Clinical Medicine
Description of Research
During the past five years, Dr. Tolba has worked on development of immune therapy strategies for B-cell hematologic malignancies with particular interest in chronic lymphocytic leukemia (CLL), the most common leukemia in the Western hemisphere. A relatively slow progressing tumor with readily accessible tumor cells, CLL offers an opportunity to develop and test immunotherapeutic interventions. However, a number of profound immunologic deficiencies affecting both the B- and T-cell arms have posed a challenge to immune therapy of CLL.
Dr. Tolba’s laboratory has co-developed and adapted the use of herpes simplex virus (HSV) amplicons for gene transduction of CLL cells. Using CD40L as an effector molecule, researchers in this laboratory have shown robust induction of co-stimulatory molecules on transduced and bystander cells, and roughly one third of tested patients demonstrated the capacity to generate CTL activity. However, this capacity to elicit autologous CTL response was not universal, as more than half of the patients tested failed to mount such a response in spite of adequate up-regulation of co-stimulatory signal on both transduced and by-stander CLL cells. In addition to being a highly efficient gene transfer vector, HSV-based amplicons possess the capacity to engage and activate different elements of the innate immune system. Currently, Dr. Tolba and his colleagues are studying various aspects of HSV amplicon/innate immune interaction and how this would influence the outcome of an adaptive anti-tumor immune response. Immune therapeutic strategies targeting the innate immune system might offer an alternative pathway to bypass inherent CD8+T cell defects and effectively mount a systemic anti-tumor immune response. Dr. Tolba and his research team are currently exploring how HSV amplicon interacts with the family of TLR receptors and up-regulate NKG2D ligands on target cells.
- Co-developed and adapted the use of herpes simplex virus (HSV) amplicons for gene transduction of CLL cells
- In addition to being a highly efficient gene transfer vector, HSV-based amplicons possess the capacity to engage and activate different elements of the innate immune system
Selected Cancer-Related Publications
- Cho HM, Rosenblatt JD, Tolba K, Shin SJ, Shin DS, Calfa C, Zhang Y, Shin SU. Delivery of NKG2D Ligand Using an Anti-HER2 Antibody-NKG2D Ligand Fusion Protein Results in an Enhanced Innate and Adaptive Antitumor Response. Cancer Res 70:10121-30, 2010. Read more »
- Daubeuf S, Singh D, Tan Y, Liu H, Federoff HJ, Bowers WJ, Tolba K. HSV ICP0 recruits USP7 to modulate TLR-mediated innate response. Blood 113:3264-75, 2009. Read more »