A5050572666- Monoclonal and Polyclonal Antibodies Research
- Radiopharmaceutical Chemistry and Applications
- Medical Imaging Techniques and Applications
- CAR-T cell therapy research
- Neuroblastoma Research and Treatments
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Intraperitoneal and Appendiceal Malignancies
- Lung Cancer Research Studies
- HIV Research and Treatment
- Immunodeficiency and Autoimmune Disorders
- Cancer Research and Treatments
- Advanced Biosensing Techniques and Applications
- Neuroendocrine Tumor Research Advances
- Lymphoma Diagnosis and Treatment
- Mosquito-borne diseases and control
- Glycosylation and Glycoproteins Research
- Viral Infections and Vectors
- Hormonal Regulation and Hypertension
- Ovarian cancer diagnosis and treatment
- Synthesis and Biological Evaluation
- Hepatocellular Carcinoma Treatment and Prognosis
- Cytomegalovirus and herpesvirus research
- Nanofabrication and Lithography Techniques
- Immune Response and Inflammation
Memorial Sloan Kettering Cancer Center
2015-2024
Translational Therapeutics (United States)
2024
Kettering University
2022
National Institute of Allergy and Infectious Diseases
2012-2017
National Institutes of Health
2015-2017
University of California, Berkeley
2011
Berkeley College
2011
Recently, several neutralizing anti-HIV antibodies have been isolated from memory B cells of HIV-infected individuals. Despite extensive evidence cell dysfunction in HIV disease, little is known about the which these rare HIV-specific originate. Accordingly, we used envelope gp140 and CD4 or coreceptor (CoR) binding site (bs) mutant probes to evaluate responses peripheral blood individuals at various stages infection. In contrast non-HIV responses, against were enriched within abnormal...
Abstract The four dengue virus (DENV) serotypes cause fever and hemorrhagic fever/dengue shock syndrome. Although severe disease has been associated with heterotypic secondary DENV infection, most infections are asymptomatic or result in classic DF. role of cross-reactive immunity mediating cross-protection against infection is not well understood. IFN-α/β IFN-γ receptor-deficient (AG129) mice reproduces key features human disease. We previously demonstrated a for pre-existing Abs,...
Despite the overwhelming benefits of antiretroviral therapy (ART) in curtailing viral load HIV-infected individuals, ART does not fully restore cellular and humoral immunity. individuals under show reduced responses to vaccination infections are unable mount an effective antiviral immune response upon cessation. Many factors contribute these defects, including persistent inflammation, especially lymphoid tissues, where T follicular helper (Tfh) cells instruct help B launch response. In this...
T cell–bispecific antibody antitumor function is maximized through optimal interdomain spacing and dual cis-configurations.
Background T cell-based immunotherapies using chimeric antigen receptors (CAR) or bispecific antibodies (BsAb) have produced impressive responses in hematological malignancies. However, major hurdles remained, including cytokine release syndrome, neurotoxicity, on-target off-tumor effects, reliance on autologous cells, and failure most solid tumors. BsAb armed cells offer a safe alternative. Methods We generated ex vivo (EATs) IgG-[L]-scFv-platformed BsAb, where the anti-CD3 (huOKT3) scFv...
EBV infection is associated with a number of malignancies clinical unmet need, including Hodgkin lymphoma, nasopharyngeal carcinoma, gastric cancer, and posttransplant lymphoproliferative disease (PTLD), all which express the protein latent membrane 2A (LMP2A), an antigen that difficult to target by conventional antibody approaches. To overcome this, we utilized phage display technology structure-guided selection strategy generate human T cell receptor-like (TCR-like) monoclonal antibodies...
Changes in adaptive immune cells after chemotherapy adult acute myeloid leukemia (AML) may have implications for the success of immunotherapy. This study was designed to determine functional capacity system patients with AML who completed and are potential candidates We used response seasonal influenza vaccination as a surrogate robustness 10 complete remission post-chemotherapy performed genetic, phenotypic, characterization cell subsets. Only 2 generated protective titers vaccination,...
This is the initial report of an α-based pre-targeted radioimmunotherapy (PRIT) using 225Ac and its theranostic pair, 111In. We call our novel tumor-targeting DOTA-hapten PRIT system "proteus-DOTA" or "Pr." Herein we first results radiochemistry development, radiopharmacology, stoichiometry tumor antigen binding, including role specific activity, anti-tumor efficacy, normal tissue toxicity with Pr-PRIT approach (as α-DOTA-PRIT). A series α-DOTA-PRIT therapy studies were performed in three...
Abstract Background EGFR and/or HER2 expression in pancreatic cancers is correlated with poor prognoses. We generated homodimeric (EGFRxEGFR or HER2xHER2) and heterodimeric (EGFRxHER2) T cell-engaging bispecific antibodies (T-BsAbs) to direct polyclonal cells these antigens on tumors. Methods T-BsAbs were constructed using the 2 + IgG-[L]-scFv format bearing two anti-CD3 scFvs attached light chains of an IgG engage while retaining bivalent binding tumor both Fab arms. A arm exchange strategy...
Engineering potent bispecific antibodies from single-chain variable fragments (scFv) remains difficult due to the inherent instability and insufficient binding of scFv's compared their parental immunoglobulin format. Previously, we described a scFv-based antibody (scBA) against disialoganglioside (GD2) based on anti-GD2 murine 5F11-scFv anti-CD3 huOKT3-scFv (5F11-scBA). In this study, substituted with higher affinity (13-fold) hu3F8-scFv form hu3F8-scBA. With modification, hu3F8-scBA...
Abstract Background: PRIT is designed to deliver tumor-targeted radiation while limiting exposure healthy tissues. CD38-SADA binds CD38 and select radioisotopes chelated tetraxetan (DOTA) contains a p53-derived domain mediating the self-assembly of tetramers from monomers in reversible, concentration-dependent manner. Preclinical studies have demonstrated dose-dependent anti-tumor efficacy two-step with 177Lu-DOTA administered 48h after an initial infusion. Here, we report preclinical PK...
Immune restoration disease (IRD) can develop in HIV-infected patients following antiretroviral therapy (ART) initiation as unmasking or paradoxical worsening of opportunistic infections and, rarely, autoimmune phenomena. Although IRD usually occurs the first months ART during memory CD4 T-cell recovery, Graves' a distinctive late-onset and its pathogenesis is unclear.Seven who developed from primary HIV care clinic at National Institutes Health were retrospectively identified each was...
Peritoneal carcinomatosis (PC) is considered incurable, and more effective therapies are needed. Herein we test the hypothesis that GPA33-directed intracompartmental pretargeted radioimmunotherapy (PRIT) can cure colorectal peritoneal carcinomatosis. Nude mice were implanted intraperitoneally with luciferase-transduced GPA33-expressing SW1222 cells for aggressive (e.g., resected tumor mass 0.369 ± 0.246 g;
Several potent and broadly neutralizing Abs to HIV-1 have been isolated recently from peripheral blood B cells of infected individuals, based on prescreening Ab activity in the serum. However, little is known regarding that make circulate blood. Accordingly, we investigated most likely source, bone marrow, chronically HIV-1-infected individuals who were not receiving antiretroviral therapy. Increased frequencies plasma cells, as well cell precursors, namely preB-I preB-II, decreased mature...
e15101 Background: GD2-SADA is a bispecific fusion protein with binding domains for the tumor-associated antigen GD2 and Lutetium 177 (Lu-177)-DOTA complex, p53-derived domain that mediates tetramer self-assembly disassembly (SADA). In Step 1 of PRIT, SADA tetramers bind to GD2+ tumor cells, while unbound disassembles into renally cleared monomers. 2, radioactive payload Lu-177-DOTA delivered binds tumor-bound GD2-SADA. Here, we characterize activities range tumors Lanthanide (Ln) metal-DOTA...
Pretargeted imaging and radioimmunotherapy approaches are designed to have superior targeting properties over directly targeted antibodies but impose more complex pharmacology, which hinders efforts optimize the ligands prior human applications. Human embryonic kidney 293T cells expressing humanized single-chain variable fragment (scFv) C825 (huC825) with high-affinity for DOTA-haptens (293T-huC825) in a transmembrane-anchored format eliminated requirement use other pretargeting reagents...
Hepatitis C (HCV) treatment for patients coinfected with human immunodeficiency virus (HIV) and HCV is associated modest rates of sustained virologic response (SVR) an increased rate relapse when compared to monoinfected patients. As who attain SVR are clinically indistinguishable during treatment, where both groups have fully suppressed viral load, it has not been possible identify in advance those will relapse. Biomarkers that may distinguish differential be useful provide insight into...
Abstract Background: High-risk neuroblastoma (HRNB) has an especially poor prognosis, underscoring the need for improved treatment strategies. Two-step pretargeted radioimmunotherapy (PRIT) is investigational approach designed to deliver cytotoxic radiation cancer cells and limit off-target exposure. GD2-SADA PRIT uses GD2-SADA, a bispecific fusion protein that binds glycolipid GD2 radionuclides chelated tetraxetan (DOTA). The contains p53-derived tetramerization domain drives SADA of...