Systemic Antitumor Effect of Intratumoral Injection of Dendritic Cells in Combination with Local Photodynamic Therapy

Abstract

Purpose: Photodynamic therapy (PDT), which is used clinically for the palliative treatment of cancer, induces local tumor cell death but has no effect on tumors in untreated sites.The purpose of this study was to determine if local PDT followed by intratumoral injection of nai « ve dendritic cells (IT-DC) induces systemic antitumor immunity that can inhibit the growth of untreated as well as PDT + IT-DC^treated tumors. Experimental Design: BALB/c or C57Bl/6 mice were injected s.c. with CT26 colorectal carcinoma cells and B16 melanoma cells, respectively, and following10 to12 days of tumor growth, the tumors were treated with PDTalone or PDT followed by IT-DC or IT-PBS. In other studies, tumors were established simultaneously in both lower flanks or in one flank and in the lungs, but only one flank was treated. Results:Whereas neither PDT nor IT-DC alone was effective, PDT + IT-DC eradicated both CT26 and B16 tumors in a significant proportion of animals and prolonged the survival of mice of which the tumors were not cured. The spleens of mice treated with PDT + IT-DC contained tumorspecific cytotoxic and IFN-g-secretingTcells whereas the spleens of control groups did not. Moreover, adoptive transfer of splenocytes from successfully treated CT26 tumor-free mice protected naïve animals from a subsequent challenge with CT26, and this was mediated mainly by CD8 T cells. Most importantly, PDT plus IT-DC administered to one tumor site led to tumor regression at distant sites, including multiple lung metastases. Conclusions: PDT + IT-DC induces potent systemic antitumor immunity in mice and should be evaluated in the treatment of human cancer.

Photodynamic therapy for enhancing antitumour immunity

“…This study also revealed that the effect of this combined treatment is not limited to the treated tumour but is also effective in the control of distant growth. Similar results was published by Saji et al 72 with a combination of intratumourally injected DCs and ATX-S10 Na(II)-mediated PDT. They also observed a dramatic effect on both local and distant tumours.…”

Magnetic and pH dual-responsive mesoporous silica nanocomposites for effective and low-toxic photodynamic therapy

“…Although researches on the delivery system of photosensitizers have flourished in recent years, low enriching efficiency of photosensitizers still severely hamper the therapeutic effect of PDT. 15,16 In these researches, photosensitizer dose is always too large to guarantee the therapeutic effect in clinics, which increases potential phototoxicity to the normal tissues. Specificity and controllability of some photpsensitizers at the tumor site have been performed to improve retention; herein, we fabricated a novel magnetic mesoporous silica nanoparticle (MMSN) to deliver photosensitizer to the target site using the magnetic targeting technology.…”

Melanoma resistance to photodynamic therapy: new insights

“…The potential of this synergy was corroborated using B16 tumor model, a poorly immunogenic and highly aggressive melanoma, with strong and durable tumor-specific results (Saji, Song et al 2006). …”

“…ISPI not only exert a complete local response but also it was demonstrated the effective immune response against metastatic nodules. The immune response can also be stimulated by means of intratumoral injection of dendritic cells (DC), which combined with local photodynamic therapy induces a striking antitumor effect with potent systemic antitumor immunity (Saji, Song et al 2006). PDT creates the perfect microenvironment for tumor antigen acquisition and DCs activation, alleviating the need to do in vitro loading of DCs with tumor antigens.…”