Immunophototherapy using PDT combined with rapid intratumoral dendritic cell injection.
The capacity of photodynamic therapy (PDT) to induce localized cell death and tissue damage suggests that when applied to tumors it could create a local depot of tumor-associated antigens, which would be available for uptake and presentation to the immune system, potentially leading to improved tumor control. Dendritic cells (DCs) are the most potent cells for antigen uptake, presentation, and stimulation of the immune system. However, it is unclear whether DCs would retain their viability and functional capacity for the requisite trafficking to draining lymph nodes when adoptively transferred in close temporal and anatomic proximity to the site of PDT-induced cytotoxicity. We conducted studies of combined PDT and adoptive DC therapy, "immunophototherapy," in a female, Fisher 344 rat orthotopic mammary tumor model. Using 5-aminolevulinic acid as a pro-drug, we demonstrated kinetically favorable biologic conversion to the photosensitive protoporphyrin IX, appropriate trafficking of syngeneic bone marrow-derived DCs injected into PDT-treated tumors within 15 min of completion of therapy, and improved survival over either modality alone. These data indicate that DCs rapidly administered into the site of PDT retain their viability and functional status, supporting the further evaluation of immunophototherapy strategies.
Sur
Brandon W
BW
Division of Hematology/Oncology, Department of Medicine, School of Medicine, University of California, Irvine, CA, USA.
Nguyen
Phuong
P
Sun
Chung-Ho
CH
Tromberg
Bruce J
BJ
Nelson
Edward L
EL
D000622:Aminolevulinic Acid / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D003713:Dendritic Cells / Q000276:immunology*; D004354:Drug Screening Assays, Antitumor; D015552:Injections, Intralesional; D007700:Kinetics; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000276:immunology / Q000628:therapy*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D011916:Rats, Inbred F344; D015996:Survival Rate; D013997:Time Factors
D017319:Photosensitizing Agents; D000622:Aminolevulinic Acid