A5089532829- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Cancer Immunotherapy and Biomarkers
- Neuroblastoma Research and Treatments
- Monoclonal and Polyclonal Antibodies Research
- Cutaneous Melanoma Detection and Management
- Immune Cell Function and Interaction
- Cancer therapeutics and mechanisms
- Cancer Research and Treatments
- Toxin Mechanisms and Immunotoxins
- Lung Cancer Research Studies
- vaccines and immunoinformatics approaches
- T-cell and B-cell Immunology
- Advanced Biosensing Techniques and Applications
- Cancer, Hypoxia, and Metabolism
- Nanoplatforms for cancer theranostics
- Radiopharmaceutical Chemistry and Applications
- Cancer Genomics and Diagnostics
- Virus-based gene therapy research
- Immune cells in cancer
- Lymphoma Diagnosis and Treatment
- Hematopoietic Stem Cell Transplantation
- Neuroendocrine Tumor Research Advances
- Glioma Diagnosis and Treatment
- Click Chemistry and Applications
University of Wisconsin–Madison
2013-2024
University of Wisconsin Carbone Cancer Center
2019-2024
Highland Community College - Illinois
2019
Low-dose targeted radionuclide therapy combined with immune checkpoint inhibition enhances complete response rates in preclinical tumor models.
Abstract In situ vaccination is an emerging cancer treatment strategy that uses local therapies to stimulate a systemic antitumor immune response. We previously reported in effect when combining radiation (RT) with intratumor (IT) injection of tumor-specific immunocytokine (IC), fusion antibody and IL2 cytokine. mice bearing two tumors, we initially hypothesized delivering RT plus IT-IC the “primary” tumor would induce response causing regression “secondary” tumor. To test this, one or...
<h3>Background</h3> Unlike some adult cancers, most pediatric cancers are considered immunologically cold and generally less responsive to immunotherapy. While immunotherapy has already been incorporated into standard of care treatment for patients with high-risk neuroblastoma, overall survival remains poor. In a mouse melanoma model, we found that radiation tumor-specific immunocytokine generate an in situ vaccination response syngeneic mice bearing large tumors. Here, tested whether novel...
Introduction Metabolic reprogramming of cancer and immune cells occurs during tumorigenesis has a significant impact on progression. Unfortunately, current techniques to measure tumor cell metabolism require sample destruction and/or isolations that remove the spatial context. Two-photon fluorescence lifetime imaging microscopy (FLIM) autofluorescent metabolic coenzymes nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) flavin (FAD) provides in vivo images at single level. Methods Here,...
Purpose: In 2010, a Children's Oncology Group (COG) phase III randomized trial for patients with high-risk neuroblastoma (ANBL0032) demonstrated improved event-free survival (EFS) and overall (OS) following treatment an immunotherapy regimen of dinutuximab, GM-CSF, IL2, isotretinoin compared alone. Dinutuximab, chimeric anti-GD2 monoclonal antibody, acts in part via natural killer (NK) cells. Killer immunoglobulin-like receptors (KIR) on NK cells their interactions KIR-ligands can influence...
Background Current clinical trials are using radiation therapy (RT) to enhance an antitumor response elicited by high-dose interleukin (IL)-2 or immune checkpoint blockade (ICB). Bempegaldesleukin (BEMPEG) is investigational CD122-preferential IL-2 pathway agonist with prolonged in vivo half-life and preferential intratumoral expansion of T effector cells over regulatory cells. BEMPEG has shown encouraging safety efficacy when used combination PD-1 blockade. In this study, we investigated...
Background Antibody–drug conjugates (ADCs) that deliver cytotoxic drugs to tumor cells have emerged as an effective and safe anticancer therapy. ADCs may induce immunogenic cell death (ICD) promote additional endogenous antitumor immune responses. Here, we characterized the immunomodulatory properties of D3-GPC2-PBD, a pyrrolobenzodiazepine (PBD) dimer-bearing ADC targets glypican 2 (GPC2), surface oncoprotein highly differentially expressed in neuroblastoma. Methods ADC-mediated induction...
Disease recurrence is frequent in high-risk neuroblastoma (NBL) patients even after multi-modality aggressive treatment [a combination of chemotherapy, surgical resection, local radiation therapy, autologous stem cell transplantation, and cis-retinoic acid (CRA)]. Recent clinical studies have explored the use monoclonal antibodies (mAbs) that bind to disialoganglioside (GD(2)), highly expressed NBL, as a means enable immune effector cells destroy NBL via antibody-dependent cell-mediated...
In head and neck squamous cell carcinoma (HNSCC) tumors that over-expresses huEGFR, the anti-EGFR antibody, cetuximab, antagonizes tumor viability sensitizes to radiation therapy. However, immunologic interactions between cetuximab therapy are not well understood. We transduced two syngeneic murine HNSCC lines express human EGFR (MOC1- MOC2-huEGFR) in order facilitate evaluation of cetuximab. Cetuximab was capable inducing antibody-dependent cellular cytotoxicity (ADCC) MOC1- MOC2-huEGFR...
Background In the Children’s Oncology Group ANBL1221 phase 2 trial for patients with first relapse/first declaration of refractory high-risk neuroblastoma, irinotecan and temozolomide (I/T) combined either temsirolimus (TEMS) or immunotherapy (the anti-GD2 antibody dinutuximab (DIN) granulocyte macrophage colony stimulating factory (GM-CSF)) was administered. The response rate among treated I/T/DIN/GM-CSF in initial cohort (n=17) 53%; additional were enrolled to permit further evaluation...
<h3>Background</h3> The ECOG-ACRIN Cancer Research Group evaluated rituximab treatment schedules for patients with newly-diagnosed low-tumor-burden follicular-lymphoma (FL). All received 4-weekly treatments as induction therapy. Clinically-responding were randomized to receive every 13 weeks ("maintenance") vs. no additional until progression ("non-maintenance"). Based on "time-to-rituximab-failure (TTRF)", the study-committee reported there was overall-benefit maintenance in this setting....
Background The antitumor effects of external beam radiation therapy (EBRT) are mediated, in part, by an immune response. We have reported that a single fraction 12 Gy EBRT combined with intratumoral anti-GD2 hu14.18-IL2 immunocytokine (IC) generates effective situ vaccine (ISV) against GD2-positive murine tumors. This ISV is eradicating tumors sustained memory; however, it does not generate adequate abscopal response macroscopic distant Given the immune-stimulatory capacity (RT), we...
We report an in situ vaccination, adaptable to nearly any type of cancer, that combines radiotherapy targeting one tumor and intratumoral injection this site with tumor-specific antibody interleukin-2 (IL-2; 3xTx). In a phase I clinical trial, administration 3xTx (with immunocytokine fusion IL-2, hu14.18-IL2) subjects metastatic melanoma increases peripheral CD8+ T cell effector polyfunctionality. This suggests the potential for promote antitumor immunity against tumors. poorly immunogenic...
Abstract Purpose: Fc-gamma receptors (FCGRs) are expressed on immune cells, bind to antibodies, and trigger antibody-induced cell-mediated antitumor responses when tumor-reactive antibodies present. The affinity of the FCGR/antibody interaction is variable dependent upon FCGR polymorphisms. Prior studies patients with cancer treated immunotherapy indicate that polymorphisms can influence response for certain immunotherapies act via therapeutically administered mAbs or endogenous induced from...
Background Surgical resection remains an important component of multimodality treatment for most solid tumors. Neoadjuvant immunotherapy has several potential advantages, including in-situ tumor vaccination and pathologic assessment response in the surgical specimen. We previously described strategy melanoma using local radiation (RT) intratumoral injection tumor-specific anti-GD2 immunocytokine (IT-IC). Here we tested whether neoadjuvant resection, without RT, could generate immunologic...
Background Most pediatric cancers are considered immunologically cold with relatively few responding to immune checkpoint inhibition. We recently described an effective combination radio-immunotherapy treatment regimen ( c ombination a daptive- i nnate immunotherapy r egimen (CAIR)) targeting adaptive and innate immunity in 9464D-GD2, model of neuroblastoma. Here, we characterize the mechanism CAIR role major histocompatibility complex class I (MHC-I) response. Methods Mice bearing...
Killer-cell Immunoglobulin-like Receptors (KIRs) are a family of glycoproteins expressed primarily on NK cells that can regulate their function. Inhibitory KIRs recognize MHC class I molecules (KIR-ligands) as ligands. We have reported associations and KIR-ligands for patients in two mAb-based trials: 1) A Children's Oncology Group (COG) trial children with high-risk neuroblastoma randomized to immunotherapy treatment dinutuximab (anti-GD2 mAb) + GM-CSF IL2 isotretinion or isotretinoin...
Abstract Purpose: We analyzed whole transcriptome sequencing in tumors from 23 patients with stage III or IV melanoma a pilot trial of the anti-GD2 immunocytokine, hu14.18-IL2, to identify predictive immune and/or tumor biomarkers at high risk for recurrence. Experimental Design: Patients were randomly assigned receive first three monthly courses hu14.18-IL2 immunotherapy either before (Group A) after B) complete surgical resection all known diseases. Tumors evaluated by histology and...
In a syngeneic murine melanoma (MEL) model, we recently reported an in situ vaccination response to combined radiation (RT) and intra-tumoral (IT) injection of anti-GD2 hu14.18-IL2 immunocytokine (IC). This treatment resulted 71% complete durable regression 5-week tumors, tumor-specific memory T cell response, augmented systemic anti-CTLA-4 antibody checkpoint blockade. While the ability diversify anti-tumor has been reported, hypothesize that mice rendered disease-free (DF) by RT-based ISV...
Some patients with cancer treated anticancer monoclonal antibodies (mAbs) develop antidrug (ADAs) that recognize and bind the therapeutic antibody. This response may neutralize mAb, interfere mAb effector function or cause toxicities. We investigated potential influence of ADA to modify tumor-binding capability a tumor-reactive 'immunocytokine' (IC), namely, fusion protein (hu14.18-IL2) consisting humanized, tumor-reactive, anti-GD2 genetically linked interleukin 2. characterize role...
An important component of research using animal models is ensuring rigor and reproducibility. This study was prompted after two experimenters performing virtually identical studies obtained different results when syngeneic B78 murine melanoma cells were implanted into the skin overlying flank treated with an in situ vaccine (ISV) immunotherapy. Although both thought they technique, we determined that one implanting tumors intradermally (ID) other them subcutaneously (SC). Though baseline...