Camellia W. Adams
Genentech
Network
Latest external collaboration on country level. Dive into details by clicking on the dots.
Publication
Featured researches published by Camellia W. Adams.
Journal of Molecular Biology | 2002
Felix Vajdos; Camellia W. Adams; Timothy N. Breece; Leonard G. Presta; Abraham M. de Vos; Sachdev S. Sidhu
Shotgun scanning combinatorial mutagenesis was used to study the antigen-binding site of Fab2C4, a humanized monoclonal antibody fragment that binds to the extracellular domain of the human oncogene product ErbB2. Essentially all the residues in the Fab2C4 complementarity determining regions (CDRs) were alanine-scanned using phage-displayed libraries that preferentially allowed side-chains to vary as the wild-type or alanine. A separate homolog-scan was performed using libraries that allowed side-chains to vary only as the wild-type or a similar amino acid residue. Following binding selections to isolate functional clones, DNA sequencing was used to determine the wild-type/mutant ratios at each varied position, and these ratios were used to assess the contributions of each side-chain to antigen binding. The alanine-scan revealed that most of the side-chains that contribute to antigen binding are located in the heavy chain, and the Fab2C4 three-dimensional structure revealed that these residues fall into two groups. The first group consists of solvent-exposed residues which likely make energetically favorable contacts with the antigen and thus comprise the functional-binding epitope. The second group consists of buried residues with side-chains that pack against other CDR residues and apparently act as scaffolding to maintain the functional epitope in a binding-competent conformation. The homolog-scan involved subtle mutations, and as a result, only a subset of the side-chains that were intolerant to alanine substitutions were also intolerant to homologous substitutions. In particular, the 610 A2 functional epitope surface revealed by alanine-scanning shrunk to only 369 A2 when mapped with homologous substitutions, suggesting that this smaller subset of side-chains may be involved in more precise contacts with the antigen. The results validate shotgun scanning as a rapid and accurate method for determining the functional contributions of individual side-chains involved in protein-protein interactions.
Journal of Immunology | 2009
Yik Andy Yeung; Maya Leabman; Jonathan S. Marvin; Julia Qiu; Camellia W. Adams; Samantha Lien; Melissa A. Starovasnik; Henry B. Lowman
The pH-dependent binding of Igs to the neonatal FcR (FcRn) plays a critical role in the in vivo homeostasis of IgGs. Modulating the interaction between Fc and FcRn through protein engineering is one method for improving the pharmacokinetics of therapeutic Abs. Recent studies disputed the direct relationship between increasing FcRn affinity and improved pharmacokinetic properties. In this work, we studied the pharmacokinetics of two human IgG1 Fc variants in cynomolgus monkey to further clarify the affinity-pharmacokinetic relationship. First, we report a number of novel Fc point mutations and combination variants, including some with primate-specific FcRn-binding improvements. By studying these variants along with some previously described variants across a wide range of affinities, we discovered a direct correlation of pH 6 affinity improvements with neutral pH improvements, suggesting that all of the tested variants exhibit similar pH dependency in FcRn binding. We then evaluated the pharmacokinetics of variants N434A and N434W, which, respectively, gave ∼4- and 80-fold improvements in pH 6-binding affinity to both human and nonhuman primate FcRn. Surprisingly, clearance of N434W was similar to that of wild type. N434W is the first variant studied in primates that exhibits significant binding to FcRn at pH 7.4, and its clearance substantiates the principle that too much affinity improvement, i.e., beyond that of N434W, does not yield improved pharmacokinetics. In contrast, N434A exhibited a ∼2-fold decrease in clearance in cynomolgus monkey, supporting the notion that modest increases in pH 6 FcRn affinity can result in improved pharmacokinetics in primates.
PLOS ONE | 2012
Dorothy French; Benjamin C. Lin; Manping Wang; Camellia W. Adams; Theresa Shek; Kathy Hotzel; Brad Bolon; Ronald E. Ferrando; Craig Blackmore; Kurt Schroeder; Luis A. Rodríguez; Maria Hristopoulos; Rayna Venook; Avi Ashkenazi; Luc Desnoyers
The fibroblast growth factor (FGF)-FGF receptor (FGFR) signaling system plays critical roles in a variety of normal developmental and physiological processes. It is also well documented that dysregulation of FGF-FGFR signaling may have important roles in tumor development and progression. The FGFR4–FGF19 signaling axis has been implicated in the development of hepatocellular carcinomas (HCCs) in mice, and potentially in humans. In this study, we demonstrate that FGFR4 is required for hepatocarcinogenesis; the progeny of FGF19 transgenic mice, which have previously been shown to develop HCCs, bred with FGFR4 knockout mice fail to develop liver tumors. To further test the importance of FGFR4 in HCC, we developed a blocking anti-FGFR4 monoclonal antibody (LD1). LD1 inhibited: 1) FGF1 and FGF19 binding to FGFR4, 2) FGFR4–mediated signaling, colony formation, and proliferation in vitro, and 3) tumor growth in a preclinical model of liver cancer in vivo. Finally, we show that FGFR4 expression is elevated in several types of cancer, including liver cancer, as compared to normal tissues. These findings suggest a modulatory role for FGFR4 in the development and progression of hepatocellular carcinoma and that FGFR4 may be an important and novel therapeutic target in treating this disease.
Clinical Cancer Research | 2013
Cuiling Zhong; Jianyong Wang; Bing Li; Hong Xiang; Mark Ultsch; Mary Coons; Terence Wong; Nan Chiang; Suzy Clark; Robyn Clark; Leah Quintana; Peter Gribling; Eric Suto; Kai H. Barck; Racquel Corpuz; Jenny Yao; Rashi Takkar; Wyne P. Lee; Lisa A. Damico-Beyer; Richard D. Carano; Camellia W. Adams; Robert F. Kelley; Weiru Wang; Napoleone Ferrara
Purpose: Our goal was to develop a potent humanized antibody against mouse/human CXCL12. This report summarized its in vitro and in vivo activities. Experimental Design: Cell surface binding and cell migration assays were used to select neutralizing hamster antibodies, followed by testing in several animal models. Monoclonal antibody (mAb) 30D8 was selected for humanization based on its in vitro and in vivo activities. Results: 30D8, a hamster antibody against mouse and human CXCL12α, CXCL12β, and CXCL12γ, was shown to dose-dependently block CXCL12α binding to CXCR4 and CXCR7, and CXCL12α-induced Jurkat cell migration in vitro. Inhibition of primary tumor growth and/or metastasis was observed in several models. 30D8 alone significantly ameliorated arthritis in a mouse collagen-induced arthritis model (CIA). Combination with a TNF-α antagonist was additive. In addition, 30D8 inhibited 50% of laser-induced choroidal neovascularization (CNV) in mice. Humanized 30D8 (hu30D8) showed similar in vitro and in vivo activities as the parental hamster antibody. A crystal structure of the hu30D8 Fab/CXCL12α complex in combination with mutational analysis revealed a “hot spot” around residues Asn44/Asn45 of CXCL12α and part of the RFFESH region required for CXCL12α binding to CXCR4 and CXCR7. Finally, hu30D8 exhibited fast clearance in cynomolgus monkeys but not in rats. Conclusion: CXCL12 is an attractive target for treatment of cancer and inflammation-related diseases; hu30D8 is suitable for testing this hypothesis in humans. Clin Cancer Res; 19(16); 4433–45. ©2013 AACR.
Journal of Immunological Methods | 2011
Yanmei Lu; Jean-Michel Vernes; Nan Chiang; Qinglin Ou; Jiabing Ding; Camellia W. Adams; Kyu Hong; Bao-Tran Truong; Domingos Ng; Amy Shen; Gerald R. Nakamura; Qian Gong; Leonard G. Presta; Maureen Beresini; Bob Kelley; Henry B. Lowman; Wai Lee Wong; Y. Gloria Meng
Clinical response to the anti-CD20 antibody rituximab has been demonstrated to correlate with the polymorphism in the FcγRIIIa receptor where patients homozygous for the higher affinity V158 allotype showed a better response rate. This finding suggests that engineering of anti-CD20 for increased FcγRIIIa affinity could result in improved clinical outcome. To identify variants with increased affinity to FcγRIIIa, we developed quantitative assays using soluble receptors as well as engineered cell lines expressing FcγRI or FcγRIIIa on the cell surface. We assayed a set of anti-CD20 IgG(1) variants that had identical Fab regions, but alterations in the Fc regions, in both the soluble receptor-based and cell-based FcγRIIIa binding assays. We obtained similar relative binding affinity increases and assay precisions. The increase in affinity for FcγRIIIa correlated with the increase in activity in the antibody-dependent cellular cytotoxicity assay. These variants had unaltered FcγRI binding. In addition to Fcγ receptors, IgG also binds to FcRn, the receptor responsible for the long circulating half-life of IgG. The mutations in the anti-CD20 variants were previously found not to affect FcRn binding in the soluble receptor-based assays; consequently, we used anti-Her2 variants with different binding affinities to FcRn to study FcRn binding assays. We generated a cell line expressing FcRn on the cell surface to measure IgG binding and obtained similar ranking of these anti-Her2 variants in the cell-based and the soluble receptor-based FcRn binding assays. In conclusion, both the soluble receptor-based and cell-based binding assays can be used to identify IgG(1) variants with increased affinity to FcγRIIIa and unaltered affinity to FcγRI and FcRn.
Proteomics | 2011
Natalie E. Castellana; Krista McCutcheon; Victoria Pham; Kristin Harden; Allen Nguyen; Judy Young; Camellia W. Adams; Kurt Schroeder; David Arnott; Vineet Bafna; Jane L. Grogan; Jennie R. Lill
A mouse hybridoma antibody directed against a member of the tumour necrosis factor (TNF)‐superfamily, lymphotoxin‐alpha (LT‐α), was isolated from stored mouse ascites and purified to homogeneity. After more than a decade of storage the genetic material was not available for cloning; however, biochemical assays with the ascites showed this antibody against LT‐α (LT‐3F12) to be a preclinical candidate for the treatment of several inflammatory pathologies. We have successfully rescued the LT‐3F12 antibody by performing MS analysis, primary amino acid sequence determination by template proteogenomics, and synthesis of the corresponding recombinant DNA by reverse engineering. The resurrected antibody was expressed, purified and shown to demonstrate the desired specificity and binding properties in a panel of immuno‐biochemical tests. The work described herein demonstrates the powerful combination of high‐throughput informatic proteomic de novo sequencing with reverse engineering to reestablish monoclonal antibody‐expressing cells from archived protein sample, exemplifying the development of novel therapeutics from cryptic protein sources.
Archive | 2003
Camellia W. Adams; Andrew C. Chan; Craig Crowley; Henry B. Lowman; Gerald R. Nakamura; Leonard G. Presta
Cancer Immunology, Immunotherapy | 2006
Camellia W. Adams; David Edward Allison; Kelly Flagella; Leonard G. Presta; Janet Clarke; Noel Dybdal; Kathleen McKeever; Mark X. Sliwkowski
Archive | 2000
Camellia W. Adams; Leonard G. Presta; Mark X. Sliwkowski
Archive | 2005
Camellia W. Adams; Napoleone Ferrara; Ellen Filvaroff; Weiguang Mao; Leonard G. Presta; Max L. Tejada