Ben‐Quan Shen

Abstract A016: High drug-to-antibody ratio (DAR) anti-TROP2 degrader-antibody conjugate (DAC) demonstrated poor solubility at high dose level leading to the fast clearance in mice

Victor Yip, Gillie Roth, Stephanie Monson, Peter Dragovich et autres

Abstract Proteolysis-Targeting Chimeras (PROTACs) targeting BRM (SMARCA2) afford selective in vivo degradation over BRG1 (SMARCA4) and are active in BRG1 mutant xenograft tumor models. To further enhance in vivo performance, a novel BRM degrader was conjugated to an anti-TROP2 antibody to create …

A novel approach to quantitate biodistribution and transduction of adeno-associated virus gene therapy using radiolabeled AAV vectors in mice

Hongzhi Wang, Ran Li, Shraddha Sadekar, Amrita V. Kamath et autres

An understanding of recombinant adeno-associated virus (AAV) biodistribution profiles is an important element of a preclinical development program. Here, we have developed a radiolabeling strategy utilizing the co-delivery of 125 I (non-residualizing) and 111 In (residualizing) radionuclide-conjugated AAVs to provide a detailed …

Monomethyl auristatin E (MMAE), a payload for multiple antibody drug conjugates (ADCs), demonstrates differential red blood cell partitioning across human and animal species

Victor Yip, Ola M. Saad, Doug Leipold, Chunze Li et autres

Background: Monomethyl auristatin E (MMAE) has been used as a payload for several Food and Drug Administration (FDA) approved antibody-drug conjugates (ADCs).It is known that MMAE is released from the ADC following binding, internalisation and proteolytic degradation in target tissues.A striking discrepancy …

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Clinical pharmacology strategies to accelerate the development of polatuzumab vedotin and summary of key findings

Michael Z. Liao, Dan Lu, Tong Lu, Leonid Gibiansky et autres

The favorable benefit-risk profile of polatuzumab vedotin, as demonstrated in a pivotal Phase Ib/II randomized study (GO29365; NCT02257567), coupled with the need for effective therapies in relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL), prompted the need to accelerate polatuzumab vedotin development. An …

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Utilizing PK and PD Biomarkers to Guide the First-in-Human Starting Dose Selection of MTBT1466A: A Novel Humanized Monoclonal Anti-TGFβ3 Antibody for the Treatment of Fibrotic Diseases

Rajbharan Yadav, Siddharth Sukumaran, Jeff Lutman, Mayur S. Mitra et autres

MTBT1466A is a high-affinity TGFβ3-specific humanized IgG1 monoclonal antibody with reduced Fc effector function, currently under investigation in clinical trials as a potential anti-fibrotic therapy. Here, we characterized the pharmacokinetics (PK) and pharmacodynamics (PD) of MTBT1466A in mice and monkeys and predicted …

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Abstract LB242: Characterizing the fate of cancer vaccine lipoplex-RNA following intravenous injection of 14C-DOTMA-lipoplex-mRNA in mice

Victor Yip, Gillie A. Roth, Elizabeth Aparecida Ferraz da Silva Torres, Sara Wichner et autres

Abstract Messenger RNA (mRNA) has emerged as a new class of therapeutic agent delivered by a carrier lipoplex (LPX) to elicit an immune-response for treating various diseases, including cancers. However, the PK and tissue distribution of the components is not well characterized …

Data from Mechanisms of Acquired Resistance to Trastuzumab Emtansine in Breast Cancer Cells

Guangmin Li, Jun Guo, Ben‐Quan Shen, Daniela Bumbaca Yadav et autres

Abstract The receptor tyrosine kinase HER2 is overexpressed in approximately 20% of breast cancer, and its amplification is associated with reduced survival. Trastuzumab emtansine (Kadcyla, T-DM1), an antibody–drug conjugate that is comprised of trastuzumab covalently linked to the antimitotic agent DM1 through …

Supplemental Table 3 from Mechanisms of Acquired Resistance to Trastuzumab Emtansine in Breast Cancer Cells

Guangmin Li, Jun Guo, Ben‐Quan Shen, Daniela Bumbaca Yadav et autres

Differentially expressed genes in T-DM1-resistant BT-474M1 cells with respect to the parental cell line (fold change > 2 fold and P < 0.05 of individual probes for a given gene in the microarray)

Supplemental Figures and Legends from Mechanisms of Acquired Resistance to Trastuzumab Emtansine in Breast Cancer Cells

Guangmin Li, Jun Guo, Ben‐Quan Shen, Daniela Bumbaca Yadav et autres

Supplemental Figure 1. Upregulated BHLHE41 in KPL-4 TR and BT-474M1 TR cells does not confer resistance to T-DM1. Supplemental Figure 2. Flow cytometry analysis of HER2 and MDR1 expression in KPL-4 P and TR cells, and tumor derived KPL-4 TR cells. Supplemental …

Supplemental Table 4 from Mechanisms of Acquired Resistance to Trastuzumab Emtansine in Breast Cancer Cells

Guangmin Li, Jun Guo, Ben‐Quan Shen, Daniela Bumbaca Yadav et autres

Differentially expressed genes in T-DM1-resistant KPL-4 cells with respect to the parental cell line (fold change > 2-fold and P < 0.05 of individual probes for a given gene in the microarray)

Supplemental Table 2 from Mechanisms of Acquired Resistance to Trastuzumab Emtansine in Breast Cancer Cells

Guangmin Li, Jun Guo, Ben‐Quan Shen, Daniela Bumbaca Yadav et autres

KPL-4 TR vs. Parental cells, gene expression changes > 5-fold

Supplemental Table 1 from Mechanisms of Acquired Resistance to Trastuzumab Emtansine in Breast Cancer Cells

Guangmin Li, Jun Guo, Ben‐Quan Shen, Daniela Bumbaca Yadav et autres

BT-474M1 TR vs. Parental cells, gene expression changes >5-fold