A5066325130- Monoclonal and Polyclonal Antibodies Research
- Medical Imaging and Pathology Studies
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Cancer Immunotherapy and Biomarkers
- Radiopharmaceutical Chemistry and Applications
- Advanced biosensing and bioanalysis techniques
- Prostate Cancer Treatment and Research
- Nanoplatforms for cancer theranostics
- Peptidase Inhibition and Analysis
- Immune Cell Function and Interaction
- Cancer Research and Treatments
- Virus-based gene therapy research
- Lymphoma Diagnosis and Treatment
- RNA modifications and cancer
- RNA Interference and Gene Delivery
- Viral Infectious Diseases and Gene Expression in Insects
- Advanced Biosensing Techniques and Applications
- bioluminescence and chemiluminescence research
- Glycosylation and Glycoproteins Research
- Nanoparticle-Based Drug Delivery
- Cancer Genomics and Diagnostics
- High Altitude and Hypoxia
- Herpesvirus Infections and Treatments
- Photoacoustic and Ultrasonic Imaging
City of Hope
2020-2024
Beckman Research Institute
2020-2024
University of California, Los Angeles
2014-2024
City Of Hope National Medical Center
2024
Institute for Molecular Medicine
2015-2023
UCLA Health
2014
California NanoSystems Institute
2010
While chemotherapy delivery by nanocarriers has modestly improved the survival prospects of pancreatic ductal adenocarcinoma (PDAC), additional engagement immune response could be game changing. We demonstrate a nano-enabled approach for accomplishing robust anti-PDAC immunity in syngeneic mice through induction immunogenic cell death (ICD) as well interfering immunosuppressive indoleamine 2,3-dioxygenase (IDO) pathway. This is accomplished conjugating IDO inhibitor, indoximod (IND), to...
Abstract The rapidly advancing field of cancer immunotherapy is currently limited by the scarcity noninvasive and quantitative technologies capable monitoring presence abundance CD8+ T cells other immune cell subsets. In this study, we describe generation 89Zr-desferrioxamine–labeled anti-CD8 cys-diabody (89Zr-malDFO-169 cDb) for immuno-PET tracking endogenous cells. We demonstrate that a sensitive tool detecting changes in systemic tumor-infiltrating CD8 expression preclinical syngeneic...
Significance Anti-CD8 immuno-PET imaging agents provide the potential to monitor localization, migration, and expansion of CD8-expressing cells noninvasively in vivo. Shown here is successful generation functional anti-CD8 based on engineered antibodies for use a variety preclinical disease immunotherapeutic models.
The proliferation and trafficking of T lymphocytes in immune responses are crucial events determining inflammatory responses. To study whole-body lymphocyte dynamics noninvasively vivo, we generated anti-CD4 -CD8 cys-diabodies (cDbs) derived from the parental antibody hybridomas GK1.5 2.43, respectively, for (89)Zr-immuno-PET detection helper cytotoxic cell populations.Anti-CD4 cDbs were engineered, produced via mammalian expression, purified using immobilized metal affinity chromatography,...
Noninvasive and quantitative tracking of CD8
Abstract Interleukin-2 (IL-2) is a component of most protocols adoptive cell transfer (ACT) therapy for cancer, but limited by short exposure and high toxicities. NKTR-214 kinetically-engineered IL-2 receptor βγ (IL-2Rβγ)-biased agonist consisting conjugated to multiple releasable polyethylene glycol chains resulting in sustained signaling through IL-2Rβγ. We report that ACT supported increases the proliferation, homing persistence anti-tumor T cells compared with IL-2, superior antitumor...
Significance Three-dimensional microscopy in the NIR-II window (1,000 to 1,700 nm) allows noninvasive deep-tissue optical sectioning of live mammals with high spatiotemporal resolution due suppressed light scattering and reduced tissue autofluorescence. Herein, we present a structured-illumination light-sheet (NIR-II SIM) both excitation emission wavelengths NIR-IIb (1,500 nm). Integrating structured illumination into further diminished out-of-focus background improved spatial resolution,...
Tracking and imaging immune cells in vivo non-invasively would offer insights into the responses induced by vaccination. Here we report a cancer vaccine consisting of polymer-coated NaErF
Inflammatory bowel diseases (IBDs) in humans are characterized part by aberrant CD4-positive (CD4+) T-cell responses. Currently, identification of foci inflammation within the gut requires invasive procedures such as colonoscopy and biopsy. Molecular imaging with antibody fragment probes could be used to noninvasively monitor cell subsets causing intestinal inflammation. Here, GK1.5 cys-diabody (cDb), an antimouse CD4 derived from hybridoma, was a PET probe for CD4+ T cells dextran sulfate...
The CD20 cell surface antigen is expressed at high levels by over 90% of B-cell non-Hodgkin lymphomas (NHL) and the target anti-CD20 monoclonal antibody rituximab. To provide more sensitive, tumor-specific PET imaging NHL, we sought to develop agents targeting CD20. <b>Methods:</b> Two recombinant rituximab fragments, a minibody (scFv-C<sub>H</sub>3 dimer; 80 kDa) modified scFv-Fc fragment (105 kDa), designed clear rapidly, were generated. Both fragments radiolabeled with <sup>124</sup>I,...
Prostate stem cell antigen (PSCA) is expressed on the surface in 83%–100% of local prostate cancers and 87%–100% cancer bone metastases. In this study, we sought to develop immunoPET agents using <sup>124</sup>I- <sup>89</sup>Zr-labeled anti-PSCA A11 minibodies (scFv-C<sub>H</sub>3 dimer, 80 kDa) evaluate their use for quantitative imaging cancer. <b>Methods:</b> minibody was alternatively labeled with or <sup>89</sup>Zr-desferrioxamine injected into mice bearing either matched 22Rv1...
Most NIR-IIb fluorophores are nanoparticle-based probes with long retention (≈1 month or longer) in the body. Here, we applied a novel cross-linked coating to functionalize core/shell lead sulfide/cadmium sulfide quantum dots (PbS/CdS QDs) emitting at ≈1600 nm. The was comprised of an amphiphilic polymer followed by three crosslinked polymeric layers (P3 coating), imparting high biocompatibility and >90 % excretion QDs within 2 weeks intravenous administration. P3 -QDs were conjugated...
Prostate stem cell antigen (PSCA), a surface glycoprotein expressed in normal human prostate and bladder, is over-expressed the majority of localized cancer most bone metastases. We have previously shown that hu1G8 minibody, humanized anti-PSCA antibody fragment (single-chain Fv-C(H)3 dimer, 80 kDa), can localize specifically image PSCA-expressing xenografts at 21 h post-injection. However, humanization reformatting decreased its apparent affinity. Here, we sought to evaluate PET imaging...
Epithelial membrane protein-2 (EMP2) is upregulated in a number of tumors and therefore remains promising target for mAb-based therapy. In the current study, image-guided therapy an anti-EMP2 mAb was evaluated by PET both syngeneic immunodeficient cancer models expressing different levels EMP2 to enable better understanding its tumor uptake off accumulation clearance. The therapeutic efficacy initially high- low-expressing tumors, reduced load high EMP2-expressing 4T1 HEC-1-A tumors. To...
Noninvasive evaluation of gene transfer to specific cells or tissues will allow for long-term, repetitive monitoring transgene expression. Tissue-specific promoters that restrict the expression a tumor play vital role in cancer therapy imaging. In this study, we have developed third-generation HIV-1-based lentivirus vector carrying prostate-specific promoter monitor sustained firefly luciferase (fl) reporter living mice. The fl transcriptionally targeted is driven by an enhanced antigen...
The long circulation persistence of human serum albumin (HSA) is enabled by its domain III (DIII) interaction with the neonatal Fc receptor (FcRn). A protein scaffold based on HSA DIII was designed. To modify half life scaffold, residues H535, H510, and H464 were individually mutated to alanine. wild type (WT) variants fused anti-carcinoembryonic antigen (CEA) T84.66 diabody (Db), radiolabeled (124)I injected into xenografted athymic mice for serial PET/CT imaging. All proteins targeted...
Activated leukocyte cell adhesion molecule (ALCAM) is an immunoglobulin superfamily that aberrantly expressed in a wide variety of human tumors, including melanoma, prostate cancer, breast colorectal carcinoma, bladder cancer and pancreatic adenocarcinoma. This spectrum malignancies makes ALCAM prospective pan-cancer immunoPET target to aid detection diagnosis multiple malignancies. In this study, we assess site-specific versus non-site-specific conjugation strategies for (64)Cu-DOTA...
Abstract Purpose: Prostate stem cell antigen (PSCA) is highly expressed in local prostate cancers and cancer bone metastases its expression correlates with androgen receptor activation a poor prognosis. In this study, we investigate the potential clinical applications of immunoPET anti-PSCA A11 minibody, an antibody fragment optimized for use as imaging agent. We compare minibody to 18F-Fluoride PET scans detecting tumors evaluate ability image tumor response deprivation. Experimental...
Determination of treatment response to immunotherapy in glioblastoma multiforme (GBM) is a process which can take months. Detection CD8+ T cell recruitment the tumor with noninvasive imaging modality such as positron emission tomography (PET) may allow for characterization and early evaluation therapeutic immunotherapy. In this study, we utilized 89Zr-labeled anti-CD8 cys-diabody-PET provide proof-of-concept detect immune oncolytic herpes simplex virus (oHSV) M002 syngeneic GBM model....
Abstract Introduction: Human prostate stem cell antigen (hPSCA) is a surface protein that overexpressed in pancreatic cancer but minimally expressed normal tissues, making it ideal as therapeutic marker for targeted radiopharmaceutical therapy (TRT). Humanized anti-PSCA A2 scFv-Fc2 antibody was engineered with double mutation (A2DM, t1/2 12 h) the FcRn binding site rapid clearance through liver and reduced bone marrow toxicity to improve index. The potential of A2DM investigated imaging...
SummaryFifteen normal male and 15 female subjects living permanently at a mining town located an altitude of 14,000 ft in the central Andean plateau demonstrated elevations values serum urate, creatinine, hematocrit when compared with equal numbers sea level. Of HA group, three (20%) have urate above 8 mg/100 ml, level which deposition tissues might take place. There is high degree correlation between levels creatinine series as whole. Although mean females SL males are comparable, latter...
Developments in vector design using tissue-specific and tumor-specific promoters have led to significant improvements tumor-targeting strategies. These developments combined with the ability monitor gene expression by molecular imaging facilitated detection prolonged monitoring of disease progression small-animal models. Bioluminescence offers a convenient sensitive platform for patterns preclinical models therapy. Targeting specific subset cells/tissues via systemic delivery vectors would...