A5087512989- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- CAR-T cell therapy research
- Nanoplatforms for cancer theranostics
- Photodynamic Therapy Research Studies
- Immune cells in cancer
- Cancer Research and Treatments
- Renal cell carcinoma treatment
- interferon and immune responses
- Chemokine receptors and signaling
- Ferroptosis and cancer prognosis
- Monoclonal and Polyclonal Antibodies Research
- Immune Response and Inflammation
- Cancer Cells and Metastasis
WinnMed
2022-2025
Mayo Clinic
2022-2024
Mayo Clinic in Arizona
2023-2024
Rakuten (United States)
2019-2022
Abstract Durable T cell immunity against cancer depends on the continual replenishment of effector CD8+ cells. Thymic output has been correlated with favorable prognosis in patients across a range ages, suggesting that thymus is an important source for replenishing cells capable controlling progression. However, potential thymic mature and their regulation have not clearly defined. In this study, we identified ability single positive to gain after selection, but they are subject PD-1. We...
The complex immunosuppressive nature of solid tumor microenvironments poses a significant challenge to generating efficacious and durable anticancer responses. Photoimmunotherapy is cancer treatment strategy by which an antibody conjugated with non-toxic light-activatable dye. Following administration the conjugate binding target tumor, subsequent local laser illumination activates dye, resulting in highly specific cell membrane disruption. Here we demonstrate that photoimmunotherapy...
Abstract Seven different anti–PD-1 and PD-L1 mAbs are now widely used in the United States to treat a variety of cancer types, but no clinical trials have compared them directly. Furthermore, because many these Abs do not cross-react between mouse human proteins, preclinical models exist which consider types questions. Thus, we produced humanized PD-1 mice extracellular domains both were replaced with corresponding sequences. Using this new model, sought compare strength immune response...
Patients with advanced cancers who either do not experience initial response to or progress while on immune checkpoint inhibitors (ICIs) receive salvage radiotherapy reduce tumor burden and tumor-related symptoms. Occasionally, some patients substantial global regression a rebound of cytotoxic CD8
Abstract INTRODUCTION: Cancer cell-targeted photoimmunotherapy (PIT) is a platform technology under development for the treatment of various cancers. PIT drug + device combination that utilizes monoclonal antibodies conjugated to dye (IRDye 700DX) are activated with nonthermal red light illumination induce rapid cell death by necrosis. Binding antibody-dye conjugate cancer cells followed photoactivation elicits necrosis bound antibody conjugate, providing very high specificity. Given induced...
Abstract Cytotoxic CD8+ T cells play a key role in response to anti-PD-1/PD-L1 immune checkpoint inhibitors (ICI) therapy. However, the exact effector molecules that are regulated by PD-1 signals cytotoxic have not been completely defined. Lack of this knowledge is crucial problem addressing how overcome low clinical rate ICI When exploring why certain patients responding therapy, we found non-responders did an elevated NKG7 expression as responders The difference between and anti-PD-1...
Abstract Background: Although targeting myeloid cells has become one of the next generation targets for cancer immunotherapy, there is a lack therapeutic tools to specifically target these cells. Our group developed novel humanized PD-L1-targeting antibody, H1A, that induces PD-L1 degradation via blockade and CMTM6, therefore limiting intrinsic signaling while also preventing interactions with PD-1. In immune cell compartment, CMTM6 expression restricted cells, making primary H1A. Recently,...
Abstract Cytotoxic T cells produce interferon gamma (IFNγ), which plays a critical role in anti-microbial and anti-tumor responses. However, it is not clear whether cell-derived IFNγ directly kills infected tumor target cells, how this may be regulated. Here, we report that cell expression of the kinases TBK1 IKKε regulate cytotoxicity by suppressing ability to kill cells. In targets lacking IKKε, induces TNFR1 Z-nucleic acid sensor, ZBP1, trigger RIPK1-dependent apoptosis, largely...
<title>Abstract</title> <bold>Introduction</bold>: Immune checkpoint inhibitors (ICI) are an essential systemic therapy for advanced melanoma. However, most melanomas develop resistance to ICI. Tumor-derived soluble PD-L1 (sPD-L1) and other immunosuppressive factors drive inhibitor correlate with inferior survival. We previously showed that therapeutic plasma exchange (TPE) removes sPD-L1 from circulation. Thus, we hypothesized TPE-mediated removal of could overcome immunotherapy in...
458 Background: Immune checkpoint inhibitors (ICI) targeting PD-1/PD-L1 axis has revolutionized the therapeutic landscape of patients with advanced and locally renal cell carcinoma (RCC). However, complete response rates remain low there is a need for novel options ICI-resistant refractory RCC. Our group generated humanized anti-PD-L1 antibody, called H1A, that induces PD-L1 degradation preventing not only its interaction PD-1 but also inhibiting pro-tumorigenic intracellular signaling. In...
The intrinsic and acquired resistance to PD-1/PD-L1 immune checkpoint blockade is an important challenge for patients clinicians because no reliable tool has been developed predict individualized response immunotherapy. In this study, we demonstrate the translational relevance of ex vivo functional assay that measures tumor cell killing ability patient-derived CD8 T NK cells (referred as "cytotoxic lymphocytes," or CLs) isolated from peripheral blood with renal carcinoma. Patient-derived...
Abstract INTRODUCTION: Photoimmunotherapy (PIT) is a new cancer-targeted platform technology that utilizes photoactivatable dye (IRDye 700DX) conjugated to cancer-targeting antibody. Binding of the antibody- conjugate cancer cells followed by photoactivation with nonthermal red light elicits rapid necrosis bound antibody conjugate. In previous studies using immunocompetent mouse models, intratumoral innate and adaptive immune cell activation was observed after PIT treatment. We hypothesized...
Abstract In the last decade, therapeutic landscape of renal cell carcinoma has rapidly evolved with addition PD-1/PD-L1 immune checkpoint inhibitors in armamentarium oncologists. Despite clinical evidence improved oncological outcomes, only a minority patients experience long-lasting antitumor response and complete response. The intrinsic acquired resistance to blockade is an important challenge for clinicians as no reliable tool been developed predict individualized immunotherapy. this...
Abstract Cytotoxic T lymphocytes (CTL) are indispensable in anti-tumor immunity. Although CTLs prone to exhaustion patients with advanced cancer, cell resiliency explains the presence of tumor-reactive that less exhausted, capable cytolytic function, expansion, and rebound response immunotherapy reject metastatic malignances. However, features resilient cells have not been clearly defined. In this report, we demonstrate peripheral CX3CR1 + CD8 low mitochondrial membrane potential rebounded...
Abstract Cytotoxic T lymphocytes (CTL) are indispensable in anti-tumor immunity. Although CTLs prone to exhaustion patients with advanced cancer, cell resiliency explains the presence of tumor-reactive that less exhausted, capable cytolytic function, expansion, and rebound response immunotherapy reject metastatic malignancies. However, features resilient cells have not been clearly defined. In this report, we demonstrate peripheral CX3CR1 +CD8 +T low mitochondrial membrane potential...
Abstract Although immune checkpoint blockade that targets the PD-L1 has revolutionized treatment of human cancers, only a small proportion patients positively respond to this form treatment. A limitation these therapies is they target and inhibit PD-L1’s extracellular function, which bind its receptor on PD-1 T cells cell cytotoxicity. Recent discoveries have shown expressed tumor can signal intrinsically independently ligation promote survival. Besides cells, host myeloid been high...
Abstract Though anti-PD-1/PD-L1 immune checkpoint blockade therapy has demonstrated robust anti-tumor immunity in human patients with advanced cancers such as melanoma, only a fraction of achieved durable responses. Among all the non-responders, some responded initially but developed resistance to later treatments. This reflects an urgent need understand role PD-1 signals CD8+ T cells at priming and effector stages during tumor development for benefit immunotherapy. The controversy rapid...
<h3>Background</h3> Current PD-L1 targeting antibodies have been developed to block PD-L1's interaction with PD-1, thereby preventing inhibition of T cell cytotoxicity. However, there has limited clinical success in the treatment cancers, despite high expression PD-L1. Recent reports demonstrated that tumor-intrinsic can signal intracellularly promote survival independent PD-1 ligation, potentially explaining why some cancer patients do not respond immune checkpoint therapies. Besides tumor...
<h3>Background</h3> Our lab has identified a new PD-L1 antibody (clone H1A) with unique mechanism of action. Unlike current FDA-approved therapies that block PD-L1's interaction PD-1, H1A destabilizes at the cell surface and induces its degradation. Recent research using have demonstrated effect on human PBMCs, including increased effector T populations cytotoxicity, compared to blocking antibodies. While this data is promising, there need evaluate in an immunocompetent host....
<h3>Background</h3> PD-1/PD-L1 checkpoint blockade has led to improvements in clinical outcomes various advanced cancers. However, response rates remain low and most patients eventually present with intrinsic resistance inhibitors. There is a great need elucidate tumor-intrinsic mechanisms involved immune-evasion improve patient survival. Elevated levels of soluble PD-L1 (sPD-L1) can be detected peripheral blood are associated poor survival many cancer indications. sPD-L1 secreted by tumors...
INTRODUCTION: Cancer cell-targeted photoimmunotherapy (PIT) is a platform technology under development for the treatment of various cancers. PIT drug + device combination that utilizes monoclonal antibodies conjugated to dye (IRDye 700DX) are activated with nonthermal red light illumination induce rapid cell death by necrosis. Binding antibody-dye conjugate cancer cells followed photoactivation elicits necrosis bound antibody conjugate, providing very high specificity. Given induced...
INTRODUCTION: Photoimmunotherapy (PIT) is a new cancer-targeted platform technology that utilizes photoactivatable dye (IRDye 700DX) conjugated to cancer-targeting antibody. Binding of the antibody- conjugate cancer cells followed by photoactivation with nonthermal red light elicits rapid necrosis bound antibody conjugate. In previous studies using immunocompetent mouse models, intratumoral innate and adaptive immune cell activation was observed after PIT treatment. We hypothesized...
Abstract INTRODUCTION: Photoimmunotherapy (PIT) is an investigational anti-cancer treatment platform utilizing cell-targeted antibodies conjugated to the IR700 (IRDye 700DX®) light-excitable dye. Upon illumination with non-thermal red light, target cells bound antibody-conjugates undergo rapid necrosis. Previous work demonstrated that PIT induces features of immunogenic cell death tumor and ignites immune response against tumor. In these preclinical studies, we investigated extent which...