Director, Photodynamic Therapy Center
Roswell Park Cancer Institute
Elm and Carlton Streets
Buffalo New York USA 14263
Tel: 716-845-4429
Fax: 716-845-8920
E-mail: Barbara.Henderson@roswellpark.org

Dr. Barbara W. Henderson joined the staff of Roswell Park Cancer Institute (RPCI) in 1970, as a Cancer Research Scientist, Division of Radiation Biology, Department of Radiation Medicine, and was appointed Member, Photodynamic Therapy (PDT) Center in 1999. She also is Program Leader, Biophysical Therapies Program, Cancer Center Support Grant, Research Professor, Molecular & Cellular Biophysics Program, Roswell Park Graduate Division, University at Buffalo, and Associate Research Professor, Radiation Oncology, University at Buffalo School of Medicine & Biomedical Sciences.

Dr. Henderson earned her doctoral degree in Zoology at the University of Graz, Austria, in 1966. Dr. Henderson's laboratory research program focuses on mechanisms and strategies for optimization of photodynamic therapy (PDT); oxygen and light dependency of PDT; the effect of PDT on the host immune response against tumor; determinants of photodynamic tumor destruction; and assessing the role for PDT as a modality to increase access of therapeutic macromolecules to the tumor environment.

Dr. Henderson is a member of the American Association for Cancer Research, American Society of Photobiology, European Society of Photobiology, International Photodynamic Association, and the Radiation Research Society. Currently, she serves as a Director of the International Photodynamic Association. She is a past member of the NCI Radiation Study Section and Subcommittee D (Clinical Studies) of the NCI Initial Review Group. She is a member of numerous committees at RPCI and has authored or co-authored more than 70 journal publications, book chapters and abstracts. She is Associate Editor of the journal Photochemistry and Photobiology.

Description of Research

Photodynamic Therapy: Basic and Translational Research
The objective of this program is to devise and implement more effective approaches to Photodynamic Therapy (PDT). PDT involves the administration of a photodynamically-active drug (photosensitizer) or pro-drug followed by drug-activating visible light. This therapy has been successfully applied to both neoplastic and non-neoplastic diseases.

This research program takes place in the multidisciplinary, highly interactive environments of the Photodynamic Therapy Center and the Biophysical Therapies Program. As such, numerous lines of attack are being taken to improve both the efficacy and selectivity of PDT, including (i) the rational design, synthesis and testing of new photosensitizers [directed by Dr. Ravindra Pandey], (ii) the design and application of optimal therapeutic regimens, e.g., drug dosage and schedule based on phamacokinetic/pharmacodynamic studies [directed by Dr. David Bellnier], (iii) the elucidation and exploitation of PDT-induced immune responses [directed by Dr. Sandra Gollnick] and (iv) the study of multimodal approaches.

The highly complex tumor- destructive mechanisms of PDT have long been the focus of this laboratory. They consist of direct photodamage to tumor cells as well as damage to the tumor vasculature and activation of an anti-tumor immune response. All of these processes critically depend on the presence of oxygen in the treatment environment. Current research can be summarized as outlined below:

1. PDT-induced vascular permeability can be exploited to aid in the delivery to tumor tissue of macromolecular therapeutics, where the vascular wall represents a major impediment to drug egress from the vasculature. The PDT approach has been found highly effective in preclinical studies for the delivery of the chemotherapeutic agent doxorubicin carried by liposomes1, and is being further pursued for the delivery of other macromolecular agents such as monoclonal antibodies.
2. Novel light treatment approaches are being devised that allow the manipulation of the oxygenation status of the tumor, thus influencing all components of the PDT response. Preclinical2 and clinical3 studies have revealed the critical importance of choosing the optimal light dose rate for treatment.
3. The local and systemic inflammatory response associated with PDT, long thought to be a major factor contributing to treatment outcome, has been re-evaluated and shown to be highly dependent on treatment regime4,5. The influence of “danger signals” elaborated by PDT on the activation of the adaptive immune response is being studied in collaboration with the Gollnick laboratory.
4. PDT has been found to disrupt cytokine signaling in cells and block their response to cytokine challenge. The molecular mechanisms and consequences of these PDT effects are being investigated in a collaborative effort with the laboratory of Dr. Heinz Baumann.
   In this translational research, a wide range of methodologies is used: photobiological studies at the molecular, cellular and tissue levels, assessment of tissue oxygenation using polarographic probes and hypoxia markers, functional MRI, intravital microscopy, and co-operative clinical trials.

Selected Publications

1. Snyder, J. W., Greco, W. R., Bellnier, D. A., Vaughan, L., and Henderson, B. W. Photodynamic therapy: A means to enhanced drug delivery to tumors. Cancer Res, 63: 8126-8131, 2003.
2. Sitnik, T. M., Hampton, J. A., and Henderson, B. W. Reduction of tumor oxygenation during and after photodynamic therapy in vivo: Effects of fluence rate. Br.J.Cancer, 77: 1386-1394, 1998.
3. Henderson, B. W., Busch, T. M., Vaughan, L. A., Frawley, N. P., Babich, D., Sosa, T. A., Zolo, J. D., Dee, A. S., Cooper, M. T., Bellnier, D. A., Greco, W. R., and Oseroff, A. R. Photofrin photodynamic therapy can significantly deplete or preserve oxygenation in human basal cell carcinomas during treatment, depending on fluence rate. Cancer Res., 60: 525-529, 2000.
4. Gollnick, S. O., Evans, S. S., Baumann, H., Owczarczak, B., Maier, P., Vaughan, L., Wang, W. C., Unger, E., and Henderson, B. W. Role of chemokines in the long-term response to photodynamic therapy. Brit.J.Cancer, 88: 1772-1779, 2003.
5. Henderson, B. W., Gollnick, S. O., Snyder, J. W., Busch, T. M., Kousis, P. C., Cheney, R. T., and Morgan, J. Choice of oxygen-conserving treatment regimen determines the inflammatory response and outcome of photodynamic therapy of tumors. Cancer Res, in press: 2004.