6 results on '"Rick Powers"'
Search Results
2. Supplementary Figures S1-S7 from LRRC15 Is a Novel Mesenchymal Protein and Stromal Target for Antibody–Drug Conjugates
- Author
-
Debra T. Chao, Eric D. Hsi, Susan E. Morgan-Lappe, Kurt Gish, Diane Hollenbaugh, Sasmita Mishra, Joann P. Palma, Dong Zhang, Josue Samayoa, Subashri Kumar, Thomas McGonigal, Kelly Foster, Rick Powers, Tamar Uziel, Lisa Durkin, Mien Sho, Melvin Fox, Jonathan Hickson, Sonia G. Tanlimco, and James W. Purcell
- Abstract
Figures S1-S7 show LRRC15 RNA and protein expression in cancer, and demonstrate the anti-tumor efficacy of the LRRC15-targeted ADC ABBV-085 in vitro and in vivo as a monotherapy and in combination with standard-of-care therapies.
- Published
- 2023
3. Supplementary Figure Legends from LRRC15 Is a Novel Mesenchymal Protein and Stromal Target for Antibody–Drug Conjugates
- Author
-
Debra T. Chao, Eric D. Hsi, Susan E. Morgan-Lappe, Kurt Gish, Diane Hollenbaugh, Sasmita Mishra, Joann P. Palma, Dong Zhang, Josue Samayoa, Subashri Kumar, Thomas McGonigal, Kelly Foster, Rick Powers, Tamar Uziel, Lisa Durkin, Mien Sho, Melvin Fox, Jonathan Hickson, Sonia G. Tanlimco, and James W. Purcell
- Abstract
Supplementary Figure Legends
- Published
- 2023
4. Data from LRRC15 Is a Novel Mesenchymal Protein and Stromal Target for Antibody–Drug Conjugates
- Author
-
Debra T. Chao, Eric D. Hsi, Susan E. Morgan-Lappe, Kurt Gish, Diane Hollenbaugh, Sasmita Mishra, Joann P. Palma, Dong Zhang, Josue Samayoa, Subashri Kumar, Thomas McGonigal, Kelly Foster, Rick Powers, Tamar Uziel, Lisa Durkin, Mien Sho, Melvin Fox, Jonathan Hickson, Sonia G. Tanlimco, and James W. Purcell
- Abstract
Progress in understanding tumor stromal biology has been constrained in part because cancer-associated fibroblasts (CAF) are a heterogeneous population with limited cell-type–specific protein markers. Using RNA expression profiling, we identified the membrane protein leucine-rich repeat containing 15 (LRRC15) as highly expressed in multiple solid tumor indications with limited normal tissue expression. LRRC15 was expressed on stromal fibroblasts in many solid tumors (e.g., breast, head and neck, lung, pancreatic) as well as directly on a subset of cancer cells of mesenchymal origin (e.g., sarcoma, melanoma, glioblastoma). LRRC15 expression was induced by TGFβ on activated fibroblasts (αSMA+) and on mesenchymal stem cells. These collective findings suggested LRRC15 as a novel CAF and mesenchymal marker with utility as a therapeutic target for the treatment of cancers with LRRC15-positive stromal desmoplasia or cancers of mesenchymal origin. ABBV-085 is a monomethyl auristatin E (MMAE)-containing antibody–drug conjugate (ADC) directed against LRRC15, and it demonstrated robust preclinical efficacy against LRRC15 stromal-positive/cancer-negative, and LRRC15 cancer-positive models as a monotherapy, or in combination with standard-of-care therapies. ABBV-085′s unique mechanism of action relied upon the cell-permeable properties of MMAE to preferentially kill cancer cells over LRRC15-positive CAF while also increasing immune infiltrate (e.g., F4/80+ macrophages) in the tumor microenvironment. In summary, these findings validate LRRC15 as a novel therapeutic target in multiple solid tumor indications and support the ongoing clinical development of the LRRC15-targeted ADC ABBV-085.Significance: These findings identify LRRC15 as a new marker of cancer-associated fibroblasts and cancers of mesenchymal origin and provide preclinical evidence for the efficacy of an antibody-drug conjugate targeting the tumor stroma. Cancer Res; 78(14); 4059–72. ©2018 AACR.
- Published
- 2023
5. LRRC15 Is a Novel Mesenchymal Protein and Stromal Target for Antibody-Drug Conjugates
- Author
-
James W. Purcell, Subashri Kumar, Lisa Durkin, Susan E. Morgan-Lappe, Tamar Uziel, Mien Sho, Sasmita Mishra, Melvin Fox, Kelly Foster, Josue Samayoa, Diane Hollenbaugh, Dong Zhang, Rick Powers, Sonia Tanlimco, Thomas McGonigal, Debra Chao, Kurt C. Gish, Jonathan Hickson, Joann P. Palma, and Eric D. Hsi
- Subjects
0301 basic medicine ,Male ,Cancer Research ,Stromal cell ,Immunoconjugates ,Mice, SCID ,Cell Line ,Rats, Sprague-Dawley ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Cell Line, Tumor ,Neoplasms ,Tumor Microenvironment ,Medicine ,Animals ,Humans ,Tumor microenvironment ,business.industry ,Melanoma ,Mesenchymal stem cell ,Antibodies, Monoclonal ,Membrane Proteins ,Mesenchymal Stem Cells ,Sarcoma ,Fibroblasts ,medicine.disease ,HCT116 Cells ,Xenograft Model Antitumor Assays ,Desmoplasia ,Rats ,Mice, Inbred C57BL ,030104 developmental biology ,Oncology ,Monomethyl auristatin E ,chemistry ,030220 oncology & carcinogenesis ,Cancer cell ,Cancer research ,Female ,medicine.symptom ,Stromal Cells ,business ,Oligopeptides - Abstract
Progress in understanding tumor stromal biology has been constrained in part because cancer-associated fibroblasts (CAF) are a heterogeneous population with limited cell-type–specific protein markers. Using RNA expression profiling, we identified the membrane protein leucine-rich repeat containing 15 (LRRC15) as highly expressed in multiple solid tumor indications with limited normal tissue expression. LRRC15 was expressed on stromal fibroblasts in many solid tumors (e.g., breast, head and neck, lung, pancreatic) as well as directly on a subset of cancer cells of mesenchymal origin (e.g., sarcoma, melanoma, glioblastoma). LRRC15 expression was induced by TGFβ on activated fibroblasts (αSMA+) and on mesenchymal stem cells. These collective findings suggested LRRC15 as a novel CAF and mesenchymal marker with utility as a therapeutic target for the treatment of cancers with LRRC15-positive stromal desmoplasia or cancers of mesenchymal origin. ABBV-085 is a monomethyl auristatin E (MMAE)-containing antibody–drug conjugate (ADC) directed against LRRC15, and it demonstrated robust preclinical efficacy against LRRC15 stromal-positive/cancer-negative, and LRRC15 cancer-positive models as a monotherapy, or in combination with standard-of-care therapies. ABBV-085′s unique mechanism of action relied upon the cell-permeable properties of MMAE to preferentially kill cancer cells over LRRC15-positive CAF while also increasing immune infiltrate (e.g., F4/80+ macrophages) in the tumor microenvironment. In summary, these findings validate LRRC15 as a novel therapeutic target in multiple solid tumor indications and support the ongoing clinical development of the LRRC15-targeted ADC ABBV-085. Significance: These findings identify LRRC15 as a new marker of cancer-associated fibroblasts and cancers of mesenchymal origin and provide preclinical evidence for the efficacy of an antibody-drug conjugate targeting the tumor stroma. Cancer Res; 78(14); 4059–72. ©2018 AACR.
- Published
- 2018
6. E-selectin up-regulation allows for targeted drug delivery in prostate cancer
- Author
-
Vinay, Bhaskar, Debbie A, Law, Eric, Ibsen, Danna, Breinberg, Kellie M, Cass, Robert B, DuBridge, Ferdinand, Evangelista, Susan M, Henshall, Peter, Hevezi, Jennifer C, Miller, Melody, Pong, Rick, Powers, Peter, Senter, David, Stockett, Robert L, Sutherland, Ursula, von Freeden-Jeffry, Dorian, Willhite, Richard, Murray, Daniel E H, Afar, and Vanitha, Ramakrishnan
- Subjects
Male ,Immunotoxins ,Antibodies, Monoclonal ,Prostatic Neoplasms ,Antineoplastic Agents ,Mice, SCID ,Xenograft Model Antitumor Assays ,Up-Regulation ,Gene Expression Regulation, Neoplastic ,Mice ,Antibody Specificity ,Animals ,Humans ,E-Selectin ,Oligopeptides - Abstract
We have used the Eos Hu03 GeneChip array, which represents over 92% of the transcribed human genome, to measure gene expression in a panel of normal and diseased human tissues. This analysis revealed that E-selectin mRNA is selectively overexpressed in prostate cancer epithelium, a finding that correlated strongly with E-selectin protein expression as assessed by immunohistochemistry. Antibodies against E-selectin that blocked function failed to impede cancer cell growth, suggesting that overexpression of E-selectin was not essential for cell growth. However, a novel auristatin E-based antibody drug conjugate (ADC), E-selectin antibody valine-citrulline monomethyl-auristatin E, was a potent and selective agent against E-selectin-expressing cancer cell lines in vitro, with the degree of cytotoxicity varying with surface antigen density. Interestingly, sensitivity to the ADC differed among cell lines from different tissues expressing similar amounts of E-selectin and was found to correlate with sensitivity to free auristatin E. Furthermore, E-selectin-expressing tumors grown as xenografts in severe combined immunodeficient mice were responsive to treatment with E-selectin antibody valine-citrulline monomethyl-auristatin E in vivo, with more than 85% inhibition of tumor growth observed in treated mice. These findings demonstrate that an E-selectin-targeting ADC has potential as a prostate cancer therapy and validates a genomics-based paradigm for the identification of cancer-specific antigens suitable for targeted therapy.
- Published
- 2003
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.