Geoffrey Del Rosario

Antibody-Mediated Delivery of BRM/BRG1 Protein Degraders Affords Strong Antitumor Efficacy in Multiple BRM-Dependent Non-Small Cell Lung Cancer Xenograft Models

Summer A. Baker Dockrey, Pravin Chandra, Huifen Chen, Shu Chen et autres

The synthesis and biological characterization of multiple degrader antibody conjugates (DACs) bearing a heterobifunctional VHL-dependent proteolysis targeting chimera (PROTAC) payload is described. The conjugated molecule (A515) potently and extensively degrades the BRM protein (also known as SMARCA2) in cell-based assessments and exhibits …

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Measurement of specific and nonspecific tissue uptake of antibodies in tumor by SPECT imaging and nonlinear compartmental modeling

Nicholas S. Cho, Jason Ho, Geoffrey Del Rosario, Shang‐Fan Yu et autres

Understanding the mechanisms driving specific and nonspecific tissue uptake of antibodies can inform protein engineering strategies that maximize therapeutic efficacy in target tissues while minimizing off-target tissue toxicities. While in vitro cell assays are typically used to study these internalization mechanisms, there …

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Abstract 2577: Analyzing specific and nonspecific tissue uptake of antibodies by SPECT imaging and non-linear compartmental modeling

Nicholas S. Cho, Phillip Spinosa, Danielle Mandikian, Geoffrey Del Rosario et autres

Abstract Understanding the mechanisms driving specific target engagement versus off-target nonspecific cellular uptake of antibodies can help inform design and/or delivery strategies that maximize therapeutic indices. Receptor binding kinetics, rates of receptor-mediated internalization and nonspecific pinocytosis are often measured through in vitro …

Determining the conditions for robust acidoCEST MRI to measure extracellular pH in tumors in vivo

Rohan S. Virgincar, Kai Barck, Mary Ann T. Go, Geoffrey Del Rosario et autres

AcidoCEST MRI is a promising technique to directly measure extracellular pH in vivo and is well-suited to imaging tumors, which can exhibit acidosis. However, few studies have demonstrated the conditions and the minimum contrast agent concentrations needed for robust acidoCEST MRI. In …

Supplementary Data from Calicheamicin Antibody–Drug Conjugates with Improved Properties

Breanna S. Vollmar, Chris Frantz, Melissa M. Schutten, Fiona Zhong et autres

Supplementary Data

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Supplementary Data from Calicheamicin Antibody–Drug Conjugates with Improved Properties

Breanna S. Vollmar, Chris Frantz, Melissa M. Schutten, Fiona Zhong et autres

Supplementary Data

Data from Calicheamicin Antibody–Drug Conjugates with Improved Properties

Breanna S. Vollmar, Chris Frantz, Melissa M. Schutten, Fiona Zhong et autres

Abstract Calicheamicin antibody–drug conjugates (ADCs) are effective therapeutics for leukemias with two recently approved in the United States: Mylotarg (gemtuzumab ozogamicin) targeting CD33 for acute myeloid leukemia and Besponsa (inotuzumab ozogamicin) targeting CD22 for acute lymphocytic leukemia. Both of these calicheamicin ADCs …

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Data from Calicheamicin Antibody–Drug Conjugates with Improved Properties

Breanna S. Vollmar, Chris Frantz, Melissa M. Schutten, Fiona Zhong et autres

Abstract Calicheamicin antibody–drug conjugates (ADCs) are effective therapeutics for leukemias with two recently approved in the United States: Mylotarg (gemtuzumab ozogamicin) targeting CD33 for acute myeloid leukemia and Besponsa (inotuzumab ozogamicin) targeting CD22 for acute lymphocytic leukemia. Both of these calicheamicin ADCs …

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Data from An Anti–CD22-seco-CBI-Dimer Antibody–Drug Conjugate (ADC) for the Treatment of Non-Hodgkin Lymphoma That Provides a Longer Duration of Response than Auristatin-Based ADCs in Preclinical Models

Shang‐Fan Yu, Donna W. Lee, Bing Zheng, Geoffrey Del Rosario et autres

Abstract We are interested in developing a second generation of antibody–drug conjugates (ADCs) for the treatment of non-Hodgkin lymphoma (NHL) that could provide a longer duration of response and be more effective in indolent NHL than the microtubule-inhibiting ADCs pinatuzumab vedotin [anti–CD22-vc-monomethyl …

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Supplementary Data from An Anti–CD22-seco-CBI-Dimer Antibody–Drug Conjugate (ADC) for the Treatment of Non-Hodgkin Lymphoma That Provides a Longer Duration of Response than Auristatin-Based ADCs in Preclinical Models

Shang‐Fan Yu, Donna W. Lee, Bing Zheng, Geoffrey Del Rosario et autres

Supplementary Data

Data from An Anti–CD22-seco-CBI-Dimer Antibody–Drug Conjugate (ADC) for the Treatment of Non-Hodgkin Lymphoma That Provides a Longer Duration of Response than Auristatin-Based ADCs in Preclinical Models

Shang‐Fan Yu, Donna W. Lee, Bing Zheng, Geoffrey Del Rosario et autres

Abstract We are interested in developing a second generation of antibody–drug conjugates (ADCs) for the treatment of non-Hodgkin lymphoma (NHL) that could provide a longer duration of response and be more effective in indolent NHL than the microtubule-inhibiting ADCs pinatuzumab vedotin [anti–CD22-vc-monomethyl …

Supplementary Data from An Anti–CD22-seco-CBI-Dimer Antibody–Drug Conjugate (ADC) for the Treatment of Non-Hodgkin Lymphoma That Provides a Longer Duration of Response than Auristatin-Based ADCs in Preclinical Models

Shang‐Fan Yu, Donna W. Lee, Bing Zheng, Geoffrey Del Rosario et autres

Supplementary Data