Near-infrared photoimmunotherapy (NIR-PIT) is a newly developed and promising therapy that specifically destroys target cells by irradiating antibody-photo-absorber conjugates (APCs) with NIR light. ...APCs bind to target molecules on the cell surface, and when exposed to NIR light, cause disruption of the cell membrane due to the ligand release reaction and dye aggregation. This leads to rapid cell swelling, blebbing, and rupture, which leads to immunogenic cell death (ICD). ICD activates host antitumor immunity, which assists in killing still viable cancer cells in the treated lesion but is also capable of producing responses in untreated lesions. In September 2020, an APC and laser system were conditionally approved for clinical use in unresectable advanced head and neck cancer in Japan, and are now routine in appropriate patients. However, most tumors have been relatively accessible in the oral cavity or neck. Endoscopes offer the opportunity to deliver light deeper within hollow organs of the body. In recent years, the application of endoscopic therapy as an alternative to surgery for the treatment of cancer has expanded, providing significant benefits to inoperable patients. In this review, we will discuss the potential applications of endoscopic NIR-PIT, especially in thoracic and gastrointestinal cancers.
Near‐infrared photoimmunotherapy (NIR‐PIT) is a novel cancer therapy that employs a combination of infrared light and tumor‐targeted monoclonal antibody‐photoabsorber conjugates to cause both direct ...tumor necrosis and immunogenic cell death. NIR‐PIT may have potential in the perioperative setting before surgery, and therefore it is important to know the effect of NIR‐PIT on wound healing. Fifty mice were implanted with subcutaneous xenografts of N87 human gastric cancer cells, and tumors were excised after reaching a predetermined size. After excision, 30 mice were split into three groups: Controls, NIR‐PIT 1 day prior to surgery and NIR‐PIT 3 days prior to surgery. The quantity of reactive oxygen species (ROS) in each wound was measured on Postoperative Days 2 and 4, and mice were monitored weekly for 4 weeks for evidence of local tumor recurrence as well as clinical evidence of wound healing complications (eg, dehiscence, infection). The remaining 20 mice (10 controls, 10 treated with NIR‐PIT 1 day prior to surgery) were sacrificed on either Postoperative Day 7 or 14, the skin around wounds were excised, and tensile strength was measured with a digital force gauge. There were no significant differences between treatment and control groups with respect to wound ROS levels, wound tensile strength, local tumor recurrence, or postoperative complication rates (P > .05). In conclusion, neoadjuvant (pre‐operative) NIR‐PIT shows no evidence of adverse wound healing effects, and it is likely a safe adjunctive treatment to surgery. Postoperative use of NIR‐PIT merits investigation.
Near‐infrared photoimmunotherapy (NIR‐PIT), which is now under world‐wide phase 3 trial including in Japan, may be useful in the perioperative setting either before or after tumor excision that should be rational because NIR‐PIT could minimize tumor volume and initiate host antitumor immunity for safe and successful outcome. In order to apply this neoadjuvant NIR‐PIT before the surgery, only the concern of surgeons is if wound healing is hampered by preoperative NIR‐PIT. Therefore, in this study, in order to respond high demands from many surgeons, the effect of NIR‐PIT on wound healing was measured using reactive oxygen species monitoring and wound tensile strength measurements and shown to have no difference between treatment and control mice.
Background/Aim: Kinesin family member 15 (KIF15) participates in the transport of macromolecules in essential cellular processes. In this study we evaluated the clinical relevance of KIF15 expression ...in hepatocellular carcinoma (HCC). Materials and Methods: Association between KIF15 expression and clinical outcomes in HCC patients was analyzed using three independent cohorts. Localization of KIF15 expression was assessed by immunohistochemical analysis. Co-culture experiments were performed using healthy donor peripheral blood mononuclear cells (PBMC) and HCC cell lines. Results: Immunohistochemical analysis showed that KIF15 was mainly expressed in inflammatory monocytes around cancer cells. Multivariate analysis indicated high KIF15 expression was an independent poor prognostic factor for survival. HCC cells with high expression of minichromosome maintenance protein 2 (MCM2) were located close to KIF15-expressing inflammatory monocytes. The proliferation ability of HCC cells was increased by co-culture with PBMC. Conclusion: High KIF15 expression in inflammatory monocytes in tumor tissues may serve as a prognostic marker for poor outcome in HCC.
IL15 is a potent inducer of differentiation and proliferation of CD8+ T and natural killer (NK) cells, making it a promising candidate for cancer immunotherapy. However, limited efficacy of systemic ...monotherapy utilizing intravenous IL15 suggests the needs for alternative routes of administration or combination treatment with other therapies. Near-infrared photoimmunotherapy (NIR-PIT) is a highly selective anticancer treatment that elicits a massive release of tumor antigens and immunogenic signals. Here, we investigated whether intratumoral IL15 can enhance the effectiveness of cancer cell-targeted NIR-PIT using syngeneic murine tumor models. Intratumoral injection of IL15 was more effective than intraperitoneal IL15 in vivo in suppressing tumor growth and inducing intratumoral immune responses. When the efficacy of CD44-targeted NIR-PIT was compared in vivo between IL15-secreting MC38 (hIL15-MC38) and parental MC38 tumors, the hIL15-MC38/NIR-PIT group showed the best tumor growth inhibition and survival. In addition, the hIL15-MC38/NIR-PIT group showed significant dendritic cell maturation and significant increases in the number and Granzyme B expression of tumor-infiltrating CD8+ T, NK, and natural killer T cells compared with the treated parental line. Furthermore, intratumoral IL15 injection combined with CD44-targeted NIR-PIT showed significant tumor control in MC38 and Pan02-luc tumor models. In bilateral tumor models, CD44-targeted NIR-PIT in hIL15-MC38 tumors significantly suppressed the growth of untreated MC38 tumors, suggesting abscopal effects. Mice that achieved complete response after the combination therapy completely rejected later tumor rechallenge. In conclusion, local IL15 administration synergistically improves the efficacy of cancer cell-targeted NIR-PIT probably by inducing stronger anticancer immunity, indicating its potential as an anticancer treatment strategy.
Interleukin (IL)-15 is a potent inducer of differentiation and proliferation of CD8
+
T and natural killer (NK) cells, making it a promising candidate for cancer immunotherapy. However, limited ...efficacy of systemic monotherapy utilizing intravenous IL-15 suggests needs for alternative routes of administration or combination treatment with other therapies. Near-infrared photoimmunotherapy (NIR-PIT) is a highly selective anti-cancer treatment that elicits massive release of tumor antigens and immunogenic signals. Here, we investigated whether intratumoral IL-15 can enhance the effectiveness of cancer cell-targeted NIR-PIT using syngeneic murine tumor models. Intratumoral injection of IL-15 was more effective than intraperitoneal IL-15
in vivo
in suppressing tumor growth and inducing intratumoral immune responses. When the efficacy of CD44-targeted NIR-PIT was compared
in vivo
between IL-15-secreting MC38 (hIL-15-MC38) and parental MC38 tumors, the hIL-15-MC38/NIR-PIT group showed the best tumor growth inhibition and survival. Additionally, the hIL-15-MC38/NIR-PIT group showed significant dendritic cell maturation and significant increases in the number and Granzyme B expression of tumor-infiltrating CD8
+
T, NK, and natural killer T cells compared to the treated parental line. Furthermore, intratumoral IL-15 injection combined with CD44-targeted NIR-PIT showed significant tumor control in MC38 and Pan02-luc tumor models. In bilateral tumor models, CD44-targeted NIR-PIT in hIL-15-MC38 tumors significantly suppressed the growth of untreated MC38 tumors, suggesting abscopal effects. Mice that achieved complete response after the combination therapy completely rejected later tumor rechallenge. In conclusion, local IL-15 administration synergistically improves the efficacy of cancer cell-targeted NIR-PIT probably by inducing stronger anti-cancer immunity, indicating its potential as an anti-cancer treatment strategy.
Near-infrared photoimmunotherapy (NIR-PIT) is a new cancer treatment that uses an antibody-IRDye700DX (IR700) conjugate that binds to a target followed by the application of NIR light that results in ...dramatic changes in solubility of the conjugate leading to rapid cell membrane damage and highly immunogenic cell death. NIR-PIT has been used clinically in treating advanced head and neck cancers using an anti-EGFR antibody-IR700 conjugate and has been conditionally approved for clinical use in Japan. NIR-PIT can be employed using a wide range of targeting antibodies. Podoplanin (PDPN), also known as gp38, is a 38 kDa type-1 transmembrane protein associated with lymphatic vessels. In cancer cells and cancer-associated fibroblasts (CAFs), PDPN expression has been widely reported and correlates with poor outcomes in several cancer types. In this study, we evaluated the efficacy of PDPN-targeted NIR-PIT in syngenetic mouse models of cancer. PDPN-targeted NIR-PIT destroyed PDPN-expressing cancer cells and CAFs selectively, suppressing tumor progression and prolonging survival with minimal damage to lymphatic vessels compared with the control group. Interestingly, PDPN-targeted NIR-PIT also exerted a therapeutic effect by targeting CAFs in tumor models which do not express in cancer cells. Furthermore, increased cytotoxic T cells in the tumor bed after PDPN-targeted NIR-PIT were observed, suggesting enhanced host antitumor immunity. Thus, PDPN-targeted NIR-PIT is a promising new cancer therapy strategy for PDPN-expressing cancer cells and CAFs.
V-domain immunoglobulin suppressor of T cell activation (VISTA) is an inhibitory immune checkpoint molecule that is broadly expressed on lymphoid and myeloid cells, including regulatory T cells ...(Tregs) and myeloid-derived suppressor cells (MDSCs). Near-infrared photoimmunotherapy (NIR-PIT) is a cancer treatment that utilizes an antibody-photoabsorber (IRDye 700DX NHS ester) conjugate to selectively kill target cells after the local application of NIR light. Depletion of VISTA-expressing cells in the tumor microenvironment (TME) using NIR-PIT could enhance anti-tumor immune responses by removing immune suppressive cells. The purpose of this study was to evaluate the anti-tumor efficacy of VISTA-targeted NIR-PIT using two murine tumor models, MC38-luc and LL2-luc. VISTA was expressed on T cells including Tregs and MDSCs in the TME of these tumors. In contrast, CD45 − cells, including cancer cells, did not express VISTA. VISTA-targeted NIR-PIT depleted VISTA-expressing cells ex vivo. In vivo VISTA-targeted NIR-PIT inhibited tumor progression and prolonged survival in both models. After VISTA-targeted NIR-PIT, augmented CD8 + T cell and dendritic cell activation were observed in regional lymph nodes. In conclusion, VISTA-targeted NIR-PIT can effectively treat tumors by decreasing VISTA-expressing immune suppressor cells in the TME. Local depletion of VISTA-expressing cells in the tumor bed using NIR-PIT is a promising new cancer immunotherapy for treating various types of tumors.
Near-infrared photoimmunotherapy (NIR-PIT) is a newly developed and selective cancer treatment that induces necrotic and immunogenic cell death and utilizes a mAb conjugated to a photo-absorber dye, ...IR700DX, activated by NIR light. Although CD44 is a surface cancer marker associated with drug resistance, anti-CD44-IR700 NIR-PIT results in inhibited cell growth and prolonged survival in multiple tumor types. Meanwhile, CD25-targeted NIR-PIT has been reported to achieve selective and local depletion of FOXP3
CD25
CD4
regulatory T cells (Treg), which are primary immunosuppressive cells in the tumor microenvironment (TME), resulting in activation of local antitumor immunity. Combined NIR-PIT with CD44- and CD25-targeted agents has the potential to directly eliminate tumor cells and also amplify the immune response by removing FOXP3
CD25
CD4
Tregs from the TME. We investigated the difference in therapeutic effects of CD44-targeted NIR-PIT alone, CD25-targeted NIR-PIT alone, and the combination of CD44- and CD25-targeted NIR-PIT in several syngeneic tumor models, including MC38-luc, LL/2, and MOC1. The combined NIR-PIT showed significant tumor growth inhibition and prolonged survival compared with CD44-targeted NIR-PIT alone in all tumor models and showed prolonged survival compared with CD25-targeted NIR-PIT alone in MC38-luc and LL/2 tumors. Combined CD44- and CD25-targeted NIR-PIT also resulted in some complete remissions. Therefore, combined NIR-PIT simultaneously targeting cancer antigens and immunosuppressive cells in the TME may be more effective than either type of NIR-PIT alone and may have potential to induce prolonged immune responses in treated tumors.
Purpose
This study evaluated the efficacy and safety of transvaginal approach combined intracavitary and interstitial brachytherapy (IC/IS BT) assisted by transrectal ultrasound (TRUS) for treatment ...of locally advanced cervical cancer (LACC).
Materials and Methods
A total of 30 patients of LACC treated with external beam radiotherapy and IC/IS BT via transvaginal approach assisted by transrectal ultrasound were observed retrospectively. The 2-year local control (LC), progression-free survival (PFS), and overall survival (OS) were analyzed using the Kaplan–Meier method. Late adverse events were also evaluated to assess the safety of IC/IS BT.
Results
The median follow-up period was 22 months. The 2-year LC, PFS, and OS were 90%, 61%, and 82%, respectively. We observed no critical complications related to the IC/IS BT technique. Late adverse events of grade 3 or more included one case of grade 4 colon perforation.
Conclusion
Our patient series demonstrated that radiotherapy combined with transvaginal approach, TRUS-assisted IC/IS BT achieves favorable local control and safety for LACC.
Evaluation of lymphatic drainage can be challenging to differentiate between separate drainage basins because only one 'color' is typically employed in sentinel node studies. This study aimed to test ...the feasibility of multicolor
lymphangiography using newly developed organic polymer dots.
Biocompatible, purely organic, hydroporphyrin-doped near-infrared-emitting polymer dots were developed and evaluated for
multicolor imaging in mouse lymph nodes.
The authors demonstrated successful multicolor
fluorescence lymphangiography using polymer dots, each tuned to a different emission spectrum. This allows minimally invasive visualization of at least four separate lymphatic drainage basins using fluorescent nanoparticles, which have the potential for clinical translation.
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