Immunophototherapy Using PDT Combined with Rapid Intratumoral Dendritic Cell Injection

Abstract

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.

Photodynamic therapy of cancer: An update

“…82 DCs are activated in response to PDT 69 and migrate to tumor draining lymph nodes where they are thought to stimulate T cell activation. 69,83 Generation of CD8 + effector and memory T cells is frequently, but not always dependent upon the presence and activation of CD4 + T cells. 84 PDT induced anti-tumor immunity may 64 or may not depend on CD4 + T cells 80 and may be augmented by natural killer (NK) cells.…”

Photodynamic therapy enhancement of anti-tumor immunity

“…Induction of acute inflammation by PDT results in the maturation and activation of dendritic cells 30 and migration to the TDLNs where they are believed to stimulate T cell activation 30,31 . Studies have shown that incubation of PDT-treated tumor cells with immature DCs leads to enhanced DC maturation, activation, and ability to stimulate T cell activation 29,32 .…”

Responses of Cancer Cells Induced by Photodynamic Therapy

“…For example, using 5-aminolevulinic acid as a pro-drug, kinetically favorable biologic conversion to the photosensitive protoporphyrin IX, appropriate trafficking of syngeneic bone marrow-derived DCs injected into PDTtreated tumors within 15 min of completion of therapy, and improved survival over either modality alone [61]. Likewise, PDT tumor lysate-pulsed DC (PDT-DC) inhibited the growth of mammary EMT6 tumors to a greater extent than freeze/thawed tumor lysate-pulsed DC (FT-DC) or PDT tumor lysates; PDT-DC also showed significant anti-tumor effects against fully established (i.e., late-stage) solid tumors [64].…”

“…Mature DCs are critical for activation of tumor-specific CD8 + T cells and the induction of antitumor immunity [60]. In response to PDT, DCs are activated [46] and migrate to tumor-draining lymph nodes, where they are thought to stimulate T-cell activation [61]. Antigen presenting cells (APCs) isolated from PDT-treated mice exhibited an enhanced ability to stimulate T-cell proliferation and IFN-gamma secretion, suggesting that PDT resulted in increased APC activity [62].…”