Background DNA origami nanoparticle (DoriNano) harnesses the power of nucleic acid nanotechnology to revolutionize therapeutic cargo delivery with unparalleled precision at the nanoscale. Overcoming the limitations that have plagued traditional nanoparticle-based delivery systems, the DoriNano platform offers an array of advantages, including ease of manufacturing, stability and easy storage, ease of formulation, simple characterization, high… Continue reading 764 DNA origami vaccine (Dorivac) for cancer immunotherapy
Tag: Enzyme Kinetics and Mechanisms
720 Fc-enhanced anti-CTLA-4 antibody, botensilimabms, enhances the efficacy of multiple therapeutic modalities in immunotherapy-refractory tumor models
Background Botensilimab, a multifunctional Fc-enhanced anti-CTLA-4 antibody, promotes superior T cell priming, memory formation, intratumoral regulatory T cell (Treg) depletion, and antigen-presenting cell (APC) activation, compared to first-generation IgG1 CTLA-4 antibodies. In patients with advanced solid tumors, botensilimab +/- balstilimab (anti-PD-1), demonstrates durable clinical responses across nine different immunotherapy-resistant or poorly immunogenic tumor types. To… Continue reading 720 Fc-enhanced anti-CTLA-4 antibody, botensilimabms, enhances the efficacy of multiple therapeutic modalities in immunotherapy-refractory tumor models
665 Itestobart, a novel 4-1BB agonist single agent, demonstrates potent efficacy in PD-1 resistant advanced melanoma patients without >=grade 3 hepatotoxicity
Background Itestobart is a humanized agonistic monoclonal antibody target to 4-1BB, which plays key roles as a potent co-stimulator of both adaptive and innate immune cells. Unlike first-generation anti-4-1BB antibodies with limited clinical activity but severe dose-limiting hepatotoxicity, Itestobart recognized different epitope, activating the 4-1BB signaling pathway without interfere the binding of endogenous 4-1BB ligand… Continue reading 665 Itestobart, a novel 4-1BB agonist single agent, demonstrates potent efficacy in PD-1 resistant advanced melanoma patients without >=grade 3 hepatotoxicity
640 A phase 1/2 first in human study of ADI-270, an armored allogeneic anti-CD70 chimeric antigen receptor {gamma}{delta} T cell therapy, in patients with relapsed or refractory clear cell renal cell carcinoma
Background Cluster of differentiation 70 (CD70) is a type II transmembrane protein belonging to the tumor necrosis factor superfamily.1 In normal tissues, CD70 is transiently expressed in activated lymphocytes, including B, T, NK cells, and mature dendritic cells.2 CD70 is aberrantly expressed in solid and hematologic cancers (figure 1) and is implicated in enhanced growth,… Continue reading 640 A phase 1/2 first in human study of ADI-270, an armored allogeneic anti-CD70 chimeric antigen receptor {gamma}{delta} T cell therapy, in patients with relapsed or refractory clear cell renal cell carcinoma
495 Targeting sialylation as a novel glycoimmune checkpoint in small cell lung cancer
Background Small cell lung cancer (SCLC) is an aggressive malignancy harboring a dismal 5-year survival rate of less than 10%. In 2019, the addition of an anti-PDL1 antibody to initial platinum-etoposide chemotherapy revolutionized the standard of care after decades of ineffective chemoradiation. Nevertheless, the observed increase in patient survival with immune checkpoint blockade (ICB) remains… Continue reading 495 Targeting sialylation as a novel glycoimmune checkpoint in small cell lung cancer
451 CD40L-4-1BB can stimulate tumor infiltrating lymphocyte ex vivo expansion from melanoma core biopsies
Background Tumor-infiltrating lymphocyte (TIL) expansion ex vivo is currently performed from surgically excised tumors in culture media containing Interleukin-2 (IL-2). Targeting antigen-presenting cells through CD40 and tumor-reactive T cells through 4-1BB signaling may result in more robust anti-tumor activity. In this study we investigated the impact of coordinated CD40L and 4-1BB costimulation on ex vivo… Continue reading 451 CD40L-4-1BB can stimulate tumor infiltrating lymphocyte ex vivo expansion from melanoma core biopsies
526 Pharmacokinetic and pharmacodynamic analyses of PD-1 blockade with nivolumab at varying doses and schedules supports administration at markedly reduced dose and frequency
Background Immune checkpoint inhibitors (ICI), specifically agents blocking PD-1/PD-L1, have revolutionized cancer treatment with durable responses and improved survival in numerous malignancies. However, their unprecedented success has come with tremendous financial and logistical burden on delivery of cancer care. There is increasing interest in de-escalated dosing regimens to improve access and reduce burden. We report… Continue reading 526 Pharmacokinetic and pharmacodynamic analyses of PD-1 blockade with nivolumab at varying doses and schedules supports administration at markedly reduced dose and frequency
521 Characterization and prevalence of the novel immunomodulatory protein Siglec-15 expression in tumor cells and macrophages across multiple solid tumor indications
Background Siglec-15 is a member of the sialic acid-binding Ig-like lectins (Siglec) family and is a novel target for immunotherapy in cancer. It exhibits low expression in normal tissues but broad expression across cancer indications, specifically on tumor-associated macrophages (TAMs) and tumor cells.1 To characterize the potential of Siglec-15 as a therapeutic target for solid… Continue reading 521 Characterization and prevalence of the novel immunomodulatory protein Siglec-15 expression in tumor cells and macrophages across multiple solid tumor indications
515 CO-005, a novel anti-CD47 fusion protein with improved safety and efficacy in Lymphoma therapies
Background Anti-CD20 antibodies, such as rituximab, are crucial in the therapeutic strategies for nearly all subtypes of B-cell non-Hodgkin’s lymphoma (NHL). However, when these lymphomas become resistant to standard treatments, the prognosis is poor.1 CD47 blockade has emerged as a promising approach, demonstrating synergy with anti-CD20 therapies2 and inhibiting disease dissemination by blocking the CD47-SIRPα… Continue reading 515 CO-005, a novel anti-CD47 fusion protein with improved safety and efficacy in Lymphoma therapies
509 DSP216 — a novel anti HLA-GxCD47 bi-specific fusion protein for cancer immunotherapy
Background Therapeutic inhibition of CD47/SIRPα ‘don’t eat me’ signaling can reactivate innate immunity and CD47-based combination therapies demonstrated encouraging clinical efficacy.1 An interesting target for combination is HLA-G, a cancer-expressed immune checkpoint that inhibits multiple immune cell subsets and recruits suppressive immune cells to the tumor microenvironment.2 Here, we report on the preclinical characterization of… Continue reading 509 DSP216 — a novel anti HLA-GxCD47 bi-specific fusion protein for cancer immunotherapy