Karen L. Lenz

Preclinical development of SL-325, a novel high-affinity DR3-blocking antibody for durable inhibition of the DR3/TL1A axis in inflammatory bowel disease

Mahmud M. Hussain, Anne Y. Lai, Derek Franklin, Karen L. Lenz et autres

BACKGROUND: Death receptor 3 (DR3; also termed tumor necrosis factor receptor superfamily member 25 [TNFRSF25]) is the sole functional receptor for tumor necrosis factor (TNF)-like cytokine 1A (TL1A) and is constitutively expressed on effector lymphoid cells in peripheral blood and in both …

DEVELOPMENT AND CHARACTERIZATION OF SL-325, A DR3-TARGETED, ANTAGONISTIC ANTIBODY FOR THE TREATMENT OF IBD

Mahmud M. Hussain, Anne Y. Lai, Derek A. Franklin, Noah Joseph Murr et autres

DEVELOPMENT AND CHARACTERIZATION OF SL-325, A DR3-TARGETED, ANTAGONISTIC ANTIBODY FOR THE TREATMENT OF IBD

Mahmud M. Hussain, Anne Y. Lai, Derek A. Franklin, Noah Joseph Murr et autres

Abstract BACKGROUND Commonly known as Death Receptor 3 (DR3), tumor necrosis factor receptor super family 25 (TNFRSF25) is a member of the TNFR super family that binds to soluble and cell-surface expressed forms of its monogamous ligand, TL1A. Dysregulation of this key …

502 Delivery of hexameric TIGIT-Fc-LIGHT as lipid-encapsulated mRNA achieves therapeutic exposures that potentiate immune cell activation and anti-tumor activity in the setting of CPI acquired resistance

Casey W. Shuptrine, Julia Satiaputra, Noriteru Doi, Yuhui Chen et autres

Background Previously, we characterized the bispecific Fc fusion protein (TIGIT-Fc-LIGHT) that blocks the PVR checkpoint axis and agonizes TNFRs through LIGHT. In a preclinical tumor model of acquired resistance to PD-1 blockade (CT26/AR), exposure to TIGIT-Fc-LIGHT promoted antitumor activity, suggesting that immune …

us, au (code pays fourni par la source)

Data from Lipid-Encapsulated mRNAs Encoding Complex Fusion Proteins Potentiate Antitumor Immune Responses

Casey W. Shuptrine, Yuhui Chen, Jayalakshmi Miriyala, Karen L. Lenz et autres

Abstract Lipid nanoparticle (LNP)–encapsulated mRNA has been used for in vivo production of several secreted protein classes, such as IgG, and has enabled the development of personalized vaccines in oncology. Establishing the feasibility of delivering complex multispecific modalities that require higher-order structures …

Figure S1 from Lipid-Encapsulated mRNAs Encoding Complex Fusion Proteins Potentiate Antitumor Immune Responses

Casey W. Shuptrine, Yuhui Chen, Jayalakshmi Miriyala, Karen L. Lenz et autres

Supplemental Figure 1

Figure S1 from Lipid-Encapsulated mRNAs Encoding Complex Fusion Proteins Potentiate Antitumor Immune Responses

Casey W. Shuptrine, Yuhui Chen, Jayalakshmi Miriyala, Karen L. Lenz et autres

Supplemental Figure 1

Data from Lipid-Encapsulated mRNAs Encoding Complex Fusion Proteins Potentiate Antitumor Immune Responses

Casey W. Shuptrine, Yuhui Chen, Jayalakshmi Miriyala, Karen L. Lenz et autres

Abstract Lipid nanoparticle (LNP)–encapsulated mRNA has been used for in vivo production of several secreted protein classes, such as IgG, and has enabled the development of personalized vaccines in oncology. Establishing the feasibility of delivering complex multispecific modalities that require higher-order structures …

Lipid-Encapsulated mRNAs Encoding Complex Fusion Proteins Potentiate Antitumor Immune Responses

Casey W. Shuptrine, Yuhui Chen, Jayalakshmi Miriyala, Karen L. Lenz et autres

Lipid nanoparticle (LNP)-encapsulated mRNA has been used for in vivo production of several secreted protein classes, such as IgG, and has enabled the development of personalized vaccines in oncology. Establishing the feasibility of delivering complex multispecific modalities that require higher-order structures important …

us (code pays fourni par la source)

Abstract 1815: Rapid serial killing of target cells by Vγ9Vδ2 T Cells in cynomolgus macaques and humanized mice treated with a CD20-directed heterodimeric butyrophilin 2A1/3A1 fusion protein

Anne Y. Lai, L. Edwin Gonzalez, Noah Joseph Murr, Karen L. Lenz et autres

Abstract CD3-directed T cell engagers provide clinical benefit in a variety of hematologic cancers, but it remains unclear whether γδ T cells (GDT) are present at sufficient numbers to be similarly harnessed because they represent only 1-5% of the total T cell …

LIGHT (TNFSF14) Costimulation Enhances Myeloid Cell Activation and Antitumor Immunity in the Setting of PD-1/PD-L1 and TIGIT Checkpoint Blockade

Kyung Jin Yoo, Kellsey Johannes, Louis E Gonzalez, Arpita Patel et autres

Abstract Coinhibition of TIGIT (T cell immunoreceptor with Ig and ITIM domains) and PD-1/PD-L1 (PD-1/L1) may improve response rates compared with monotherapy PD-1/L1 blockade in checkpoint naive non–small cell lung cancer with PD-L1 expression >50%. TIGIT mAbs with an effector-competent Fc can …

us (code pays fourni par la source)

Abstract 4214: LIGHT (TNFSF14) costimulation with TIGIT blockade broadens the activity of checkpoint inhibitors (CPIs) into CPI refractory and resistant tumors through targeted myeloid cell and effector lymphocyte activation

Kyung Jin Yoo, Louis E Gonzalez, Kellsey Johannes, Jayalakshmi Miriyala et autres

Abstract Although increased TIGIT expression on TILs is associated with poor survival in patients with cancer, monotherapy TIGIT antibody blockade has not yet demonstrated significant clinical activity. PD-1 is commonly co-expressed on TILs, and PD-1 mediated SHP-2 signaling inhibits DNAM-1 (CD226), preventing …