Background Targeting the body’s own immune system to fight cancer has focused on activating T cells through immune checkpoint blockade (ICB). Because ICB agents work by reinvigorating pre-existing T cells, it is less likely that these agents will be effective in tumors with low levels of T cell infiltrate. Hormone receptor positive (HR+) breast cancer… Continue reading 499 Myeloid diversity in hormone receptor positive breast cancer reveals myeloid and lymphoid signaling pathways that correlate with T cell inhibition
Tag: Lipid and Membrane Biochemistry
440 Preclinical safety assessment for specificity of biotherapeutics using the membrane proteome array
AI SummaryThe Membrane Proteome Array (MPA) platform was developed to assess the specificity of monoclonal antibodies. It has been successful in identifying lead antibody candidates that do not display cross-reactivity with other proteins. The MPA has been accepted by the FDA and may be developed as a qualified Drug Development Tool.Background Rigorous specificity analysis is… Continue reading 440 Preclinical safety assessment for specificity of biotherapeutics using the membrane proteome array
457 Targeting FASN sensitizes irradiated glioblastoma to immune checkpoint blockade
AI SummaryTargeting fatty acid synthase (FASN) can enhance immune responses in irradiated glioblastoma, promoting immune cell infiltration and sensitizing the tumor to anti-PD-1 therapy. Blocking FASN restores the ability of nucleic acid sensors to induce interferon-beta (IFN-beta) and improves survival in mice treated with radiation and anti-PD-1. FASN is an attractive target to enhance the… Continue reading 457 Targeting FASN sensitizes irradiated glioblastoma to immune checkpoint blockade
493 Identification of different classes of antagonist monoclonal antibodies targeting the myeloid checkpoint CLEC-1 and their associated anti-tumoral in vivo efficacies in humanized preclinical models
Background The c-type lectin receptor CLEC-1 is a pattern recognition receptor1 expressed by endothelial and myeloid cells in mice, non-human primates, and humans. While genetic deletion of CLEC-1 in mice does not lead to any developmental defect, CLEC-1 deletion or CLEC-1 targeting using monoclonal antibodies increases damaged or necrotic cell antigen cross-presentation by cDC1 dendritic… Continue reading 493 Identification of different classes of antagonist monoclonal antibodies targeting the myeloid checkpoint CLEC-1 and their associated anti-tumoral in vivo efficacies in humanized preclinical models
426 Anti-folate receptor alpha (FR{alpha}) CoStimulatory Antigen Receptor (CoStAR™) drives distinct cytokine-mediated proliferation responses in CD4+ and CD8+ T cells
AI SummaryCoStAR enhances the proliferation of CD4+ and CD8+ T cells in response to target antigen binding. It provides a proliferative benefit to both cell types, with CD28.CD40 providing a stronger signal than CD28 alone. CoStAR-TILs can proliferate independent of cytokine support, suggesting potential clinical applications.Background ITIL-306 is a genetically engineered autologous TIL cell therapy… Continue reading 426 Anti-folate receptor alpha (FR{alpha}) CoStimulatory Antigen Receptor (CoStAR™) drives distinct cytokine-mediated proliferation responses in CD4+ and CD8+ T cells
411 Programming immunogenicity of bacterial cancer therapy with biosensor-driven encapsulation systems
Background More than a century after the development of Coley’s toxins, bacteria are re-emerging as a platform for cancer immunotherapy. In addition to advances in microbiology and immunology, the advent of synthetic biology has enabled the construction of complex genetic circuits to program bacteria for modulating the immune system. Systemic delivery is necessary for therapeutic… Continue reading 411 Programming immunogenicity of bacterial cancer therapy with biosensor-driven encapsulation systems
404 Impact of PSMA antibody or chimeric antigen receptor on phagocytosis and tumor localization by wild-type and NF-{kappa}B p50-deficient macrophages
Background Absence of the repressive NF-B p50 transcription factor subunit increases expression of pro-inflammatory M1 genes and reduces expression of M2 genes in myeloid cells. Adoptive transfer of immature myeloid cells lacking p50 (p50-IMC) slows the growth of syngeneic murine prostate cancer, pancreatic ductal carcinoma, or neuroblastoma when given after a dose of myelo-depleting 5-fluorouracil.1… Continue reading 404 Impact of PSMA antibody or chimeric antigen receptor on phagocytosis and tumor localization by wild-type and NF-{kappa}B p50-deficient macrophages
403 Tumor-infiltrating lymphocytes (TIL) with inducible and membrane-bound IL-12 exhibit superior antitumor activity in vitro
Background TIL cell therapy has shown clinical benefit for patients with solid tumors.1 2 However, an immunosuppressive tumor microenvironment (TME) may abrogate the full potential of TIL cell therapy.3 The proinflammatory cytokine IL-12, known for its capability to increase IFN- production and promote type 1 immune responses, reshapes the TME and has a potential to… Continue reading 403 Tumor-infiltrating lymphocytes (TIL) with inducible and membrane-bound IL-12 exhibit superior antitumor activity in vitro
402 Mitophagy reinvigorates exhausted CD8 T cell
Background Early exhaustion of tumor infiltrating CD8 T cells is a major obstacle that restricts the effectiveness of immunotherapy in a broader range of cancer patients.1 Mitochondrial health is a crucial factor determining the performance and endurance of CD8 T cells within the immunosuppressive tumor microenvironment (TME).2 Apart from encountering immunosuppressive signals, CD8 T cells… Continue reading 402 Mitophagy reinvigorates exhausted CD8 T cell
392 Engineering T cells to catalyze endogenous anticancer immunity
AI SummaryResearchers have developed a fusion protein strategy that enhances the function of T cells and other immune cells in order to improve the efficacy of pancreatic cancer therapy. They found that the novel protein significantly increased T cell function and also led to the maturation of dendritic cells, resulting in enhanced therapeutic efficacy in… Continue reading 392 Engineering T cells to catalyze endogenous anticancer immunity