Maltotriose Conjugation to a Chlorin Derivative Enhances the Antitumor Effects of Photodynamic Therapy in Peritoneal Dissemination of Pancreatic Cancer

Photodynamic therapy (PDT) is a noninvasive procedure involving a photosensitizing agent that is activated by light to produce reactive oxygen species (ROS) that selectively destroy tumor cells. In recent years, PDT has been used in the treatment of pancreatic cancer (PC). The antitumor effects of PDT include three main mechanisms: direct tumor cell death (necrosis, apoptosis, and autophagy), vascular destruction, and immune system activation. The present paper systematically summarizes the effects of PDT in the treatment of PC from the experimental studies to the clinical studies and discusses the mechanisms of PDT-induced PC destruction.

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A dual-labeled anti-FAP antibody for imaging and targeted photodynamic therapy of cancer associated fibroblasts in a pancreatic cancer mouse model

10.1055/s-0039-1683688 ◽

2019 ◽

Author(s):

E Smeets ◽

D Dorst ◽

S van Lith ◽

A Freimoser-Grundschober ◽

C Klein ◽

...

Keyword(s):

Pancreatic Cancer ◽

Photodynamic Therapy ◽

Mouse Model ◽

Cancer Associated Fibroblasts ◽

Photodynamic Therapy Of Cancer ◽

Targeted Photodynamic Therapy

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Metronomic photodynamic therapy using an implantable LED device and orally administered 5-aminolevulinic acid

Scientific Reports ◽

10.1038/s41598-020-79067-7 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Izumi Kirino ◽

Katsuhiko Fujita ◽

Kei Sakanoue ◽

Rin Sugita ◽

Kento Yamagishi ◽

...

Keyword(s):

Photodynamic Therapy ◽

Aminolevulinic Acid ◽

Antitumor Effects ◽

Continuous Irradiation ◽

Cancer Cell Death ◽

Long Duration ◽

Green Led ◽

Repeated Administrations ◽

532 Nm ◽

Patient Burden

AbstractMetronomic photodynamic therapy (mPDT) is a form of PDT that induces cancer cell death by intermittent continuous irradiation with a relatively weak power of light for a long duration (several days). We previously developed a wirelessly powered, fully implantable LED device and reported a significant anti-tumor effect of mPDT. Considering application in clinical practice, the method used for repeated administrations of photosensitizers required for mPDT should not have a high patient burden such as the burden of transvenous administration. Therefore, in this study, we selected 5-aminolevulinic acid (ALA), which can be administered orally, as a photosensitizer, and we studied the antitumor effects of mPDT. In mice with intradermal tumors that were orally administered ALA (200 mg/kg daily for 5 days), the tumor in each mouse was simultaneously irradiated (8 h/day for 5 days) using a wirelessly powered implantable green LED device (532 nm, 0.05 mW). Tumor growth in the mPDT-treated mice was suppressed by about half compared to that in untreated mice. The results showed that mPDT using the wirelessly powered implantable LED device exerted an antitumor effect even with the use of orally administered ALA, and this treatment scheme can reduce the burden of photosensitizer administration for a patient.

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Alkynyl N-BODIPYs as Reactive Intermediates for the Development of Dyes for Biophotonics

Chemistry Proceedings ◽

10.3390/ecsoc-24-08374 ◽

2020 ◽

Vol 3 (1) ◽

pp. 15

Author(s):

César Ray ◽

Andrés García-Sampedro ◽

Christopher Schad ◽

Edurne Avellanal-Zaballa ◽

Florencio Moreno ◽

...

Keyword(s):

Pancreatic Cancer ◽

Photodynamic Therapy ◽

Click Chemistry ◽

Cancer Cells ◽

Reactive Intermediates ◽

New Approach ◽

Pancreatic Cancer Cells ◽

Bio Imaging

A new approach for the rapid multi-functionalization of BODIPY dyes towards biophotonics is reported. It is based on novel N-BODIPYs, through reactive intermediates with alkynyl groups to be further derivatized by click chemistry. This approach has been exemplified by the development of new dyes for cell bio-imaging, which have proven to successfully internalize into pancreatic cancer cells and accumulate in the mitochondria. The in vitro suitability for photodynamic therapy (PDT) was also analyzed and confirmed our compounds to be promising PDT candidates for the treatment of pancreatic cancer.

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150 GAIA-102: a new class off-the-shelf allogeneic NK-like cells that can eliminate solid tumors

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-sitc2020.0150 ◽

2020 ◽

Vol 8 (Suppl 3) ◽

pp. A163-A163

Author(s):

Yui Harada ◽

Yoshikazu Yonemitsu

Keyword(s):

Nk Cells ◽

Solid Tumors ◽

Tumor Cells ◽

Adoptive Immunotherapy ◽

Nk Cell ◽

Peritoneal Dissemination ◽

Checkpoint Inhibitors ◽

Antitumor Effects ◽

Car T

BackgroundCancer immunotherapy has been established as a new therapeutic category since the recent success of immune checkpoint inhibitors and a type of adoptive immunotherapy, namely chimeric antigen receptor-modified T cells (CAR-T). Although CAR-T demonstrated impressive clinical results, serious adverse effects (cytokine storm and on-target off-tumor toxicity) and undefined efficacy on solid tumors are important issues to be solved. We’ve developed a cutting-edge, simple, and feeder-free method to generate highly activated and expanded human NK cells from peripheral blood (US9404083, PCT/JP2019/012744, PCT/JP2020/012386), and have been conducting further investigation why our new type of NK cells, named as GAIA-102, are so effective to kill malignant cells.MethodsCryopreserved PBMCs purchased from vendors were mixed and processed by using LOVO and CliniMACS® Prodigy (automated/closed systems). CD3+ and CD34+ cells were depleted, and the cells were cultured with high concentration of hIL-2 and 5% UltraGRO® for 14 days in our original closed system. Then, we confirmed the expression of surface markers, CD107a mobilization and cell-mediated cytotoxicity against various tumor cells and normal cells with or without monoclonal antibody drugs in vitro and antitumor effects against peritoneal dissemination model using SKOV3 in vivo.ResultsImportantly, we’ve found that our GAIA-102 exhibited CD3-/CD56bright/CD57- immature phenotype that could kill various tumor cells efficiently from various origins, including Raji cells that was highly resistant to NK cell killing. More importantly, massive accumulation, retention, infiltration and sphere destruction by GAIA-102 were affected neither by myeloid-derived suppressor cells nor regulatory T-lymphocytes. GAIA-102 was also effective in vivo to murine model of peritoneal dissemination of human ovarian cancer; thus, these findings indicate that GAIA-102 has a potential to be an ‘upward compatible’ modality over CAR-T strategy, and would be a new and promising candidate for adoptive immunotherapy against solid tumors.ConclusionsWe now just started GMP/GCTP production of this new and powerful NK cells and first-in-human clinical trials in use of GAIA-102 will be initiated on 2021.Ethics ApprovalThe animal experiments were reviewed and approved by the Institutional Animal Care and Use Committee of Kyushu University (approval nos. A30-234-0 and A30-359-0).

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An Efficient Photodynamic Therapy Treatment for Human Pancreatic Adenocarcinoma

Journal of Clinical Medicine ◽

10.3390/jcm9010192 ◽

2020 ◽

Vol 9 (1) ◽

pp. 192 ◽

Cited By ~ 5

Author(s):

Alexandre Quilbe ◽

Olivier Moralès ◽

Martha Baydoun ◽

Abhishek Kumar ◽

Rami Mustapha ◽

...

Keyword(s):

Pancreatic Cancer ◽

Photodynamic Therapy ◽

Immune System ◽

Cancer Cells ◽

Pancreatic Adenocarcinoma ◽

Cell Lines ◽

Folate Receptor ◽

Mice Model ◽

Gene And Protein Expression ◽

The Impact

To date, pancreatic adenocarcinoma (ADKP) is a devastating disease for which the incidence rate is close to the mortality rate. The survival rate has evolved only 2–5% in 45 years, highlighting the failure of current therapies. Otherwise, the use of photodynamic therapy (PDT), based on the use of an adapted photosensitizer (PS) has already proved its worth and has prompted a growing interest in the field of oncology. We have developed a new photosensitizer (PS-FOL/PS2), protected by a recently published patent (WO2019 016397-A1, 24 January 2019). This photosensitizer is associated with an addressing molecule (folic acid) targeting the folate receptor 1 (FOLR1) with a high affinity. Folate binds to FOLR1, in a specific way, expressed in 100% of ADKP or over-expressed in 30% of cases. The first objective of this study is to evaluate the effectiveness of this PS2-PDT in four ADKP cell lines: Capan-1, Capan-2, MiapaCa-2, and Panc-1. For this purpose, we first evaluated the gene and protein expression of FOLR1 on four ADKP cell lines. Subsequently, we evaluated PS2’s efficacy in our cell lines and we assessed the impact of PDT on the secretome of cancer cells and its impact on the immune system. Finally, we evaluate the PDT efficacy on a humanized SCID mouse model of pancreatic cancer. In a very interesting way, we observed a significant increase in the proliferation of activated-human PBMC when cultured with conditioned media of ADKP cancer cells subjected to PDT. Furthermore, to evaluate in vivo the impact of this new PS, we analyzed the tumor growth in a humanized SCID mice model of pancreatic cancer. Four conditions were tested: Untreated, mice (nontreated), mice with PS (PS2), mice subjected to illumination (Light only), and mice subjected to illumination in the presence of PS (PDT). We noticed that the mice subjected to PDT presented a strong decrease in the growth of the tumor over time after illumination. Our investigations have not only suggested that PS2-PDT is an effective therapy in the treatment of PDAC but also that it activates the immune system and could be considered as a real adjuvant for anti-cancer vaccination. Thus, this new study provides new treatment options for patients in a therapeutic impasse and will provide a new arsenal in the fight against PDAC.

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