A5003633105- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Cancer Research and Treatments
- Angiogenesis and VEGF in Cancer
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Cancer Immunotherapy and Biomarkers
- Phagocytosis and Immune Regulation
- Monoclonal and Polyclonal Antibodies Research
- Retinal Diseases and Treatments
- Immune Cell Function and Interaction
- Erythrocyte Function and Pathophysiology
- Biotin and Related Studies
- Nanoplatforms for cancer theranostics
- Viral Infectious Diseases and Gene Expression in Insects
- T-cell and B-cell Immunology
- Vitamin C and Antioxidants Research
- Transgenic Plants and Applications
Massachusetts Institute of Technology
2022-2024
Abstract Although co-stimulation of T cells with agonist antibodies targeting 4-1BB (CD137) improves antitumor immune responses in preclinical studies, clinical success has been limited by on-target, off-tumor activity. Here, we report the development a tumor-anchored ɑ4-1BB (ɑ4-1BB-LAIR), which consists antibody fused to collagen-binding protein LAIR. While combination treatment an (TA99) shows only modest efficacy, simultaneous depletion CD4+ boosts cure rates over 90% mice....
Anti-CTLA-4 antibodies have successfully elicited durable tumor regression in the clinic; however, long-term benefit is limited to a subset of patients for select cancer indications. The incomplete understanding their mechanism action has hindered efforts at improvement, with conflicting hypotheses proposing either antagonism CTLA-4:B7 axis or Fc effector-mediated regulatory T cell (Treg) depletion governing efficacy. Here, we report engineering nonantagonistic CTLA-4 binding domain (b1s1e2)...
Effective antitumor immunity in mice requires activation of the type I interferon (IFN) response pathway. IFNα and IFNβ therapies have proven promising humans, but suffer from limited efficacy high toxicity. Intratumoral IFN retention ameliorates systemic toxicity, given complexity signaling, it was unclear whether long-term intratumoral IFNs would promote or inhibit responses. To this end, we compared that exhibit either brief sustained after injection syngeneic mouse tumor models....
<div>Abstract<p>Although heightened intratumoral levels of reactive oxygen species (ROS) are typically associated with a suppressive tumor microenvironment, under certain conditions ROS contribute to elimination. Treatment approaches, including some chemotherapy and radiation protocols, increase cancer cell that influence their mechanism death subsequent recognition by the immune system. Furthermore, activated myeloid cells rapidly generate upon encounter pathogens or infected...
<p>Fluorescence intensities of OT-I phenotypic markers from the cross-presentation assay with IFNa</p>
<p>Bolus hydrogen peroxide is cytotoxic but rapidly cleared by cancer cells</p>
<p>Cross-presentation assay T-cell gating strategy</p>
<p>Comparison of OT-I phenotypes in cross-presentation assay after treatment with immunogenic cell stress-inducing chemotherapy</p>
<p>Cross-presentation assay myeloid cell gating strategy</p>
<p>2.5F-GOX and MSA-IFNa do not cause toxicity in mice but fail to generate anti-tumor memory</p>
<p>Characterization of recombinant glucose oxidase fusions</p>
<p>Protein sequences</p>
<p>Additional flow analysis of 2.5F-GOX dose escalation study</p>
Monoclonal antibodies targeting the programmed cell death protein 1 (PD-1) remain most prevalent cancer immunotherapy both as a monotherapy and in combination with additional therapies. Despite extensive success of anti-PD-1 monoclonal clinic, experimental relationship between binding affinity functional potency for vivo has not been reported. Anti-PD-1 higher lower than nivolumab or pembrolizumab are entering clinic show varied preclinical efficacy. Here, we explore role broad-ranging...
Abstract Although heightened intratumoral levels of reactive oxygen species (ROS) are typically associated with a suppressive tumor microenvironment, under certain conditions ROS contribute to elimination. Treatment approaches, including some chemotherapy and radiation protocols, increase cancer cell that influence their mechanism death subsequent recognition by the immune system. Furthermore, activated myeloid cells rapidly generate upon encounter pathogens or infected eliminate disease,...
Abstract Although co-stimulation of T cells with agonist antibodies targeting 4-1BB (CD137) improves antitumor immune responses in preclinical studies, clinical development has been hampered by on-target, off-tumor toxicity. Here, we report the a tumor-anchored α4-1BB (α4-1BB-LAIR), which consists an antibody fused to collagen binding protein LAIR. While combination treatment (TA99) displayed only modest efficacy, simultaneous depletion CD4 + boosted cure rates over 90% mice. We elucidated...
<h3>Background</h3> Although co-stimulation of T cells with agonist antibodies targeting 4–1BB (CD137) improves antitumor immune responses in preclinical studies, clinical development has been hampered by on-target, off-tumor toxicity. To overcome this, there a large effort to restrict activity these the tumor microenvironment using wide range strategies. Recently, we have demonstrated that fusions cytokines collagen anchoring proteins enables retention microenvironment, simultaneously...