A5086295517- Monoclonal and Polyclonal Antibodies Research
- HER2/EGFR in Cancer Research
- Cancer Cells and Metastasis
- Cell Adhesion Molecules Research
- Radiopharmaceutical Chemistry and Applications
- Streptococcal Infections and Treatments
- Estrogen and related hormone effects
- Toxin Mechanisms and Immunotoxins
- Cancer Genomics and Diagnostics
- Computational Drug Discovery Methods
- Antimicrobial Resistance in Staphylococcus
- Chemical Synthesis and Analysis
- Cancer therapeutics and mechanisms
- Enzyme Production and Characterization
- CAR-T cell therapy research
- Biofuel production and bioconversion
- Neonatal and Maternal Infections
- Glycosylation and Glycoproteins Research
- MicroRNA in disease regulation
- Advanced Breast Cancer Therapies
- RNA and protein synthesis mechanisms
- Lung Cancer Research Studies
- Microbial Metabolites in Food Biotechnology
- Immunotherapy and Immune Responses
- Cancer Treatment and Pharmacology
Pfizer (United States)
2011-2022
The University of Texas MD Anderson Cancer Center
2011
Pfizer (United Kingdom)
2011
Pearl River Community College
2007
Women's Health Research Institute
2004
Rockefeller University
1988-1992
Indian Institute of Science Bangalore
1989
Antibody-drug conjugates (ADC) are emerging as clinically effective therapy. We hypothesized that cancers treated with ADCs would acquire resistance mechanisms unique to immunoconjugate therapy and changing ADC components may overcome resistance. Breast cancer cell lines were exposed multiple cycles of anti-Her2 trastuzumab-maytansinoid (TM-ADC) at IC80 concentrations followed by recovery. The resistant cells, 361-TM JIMT1-TM, characterized cytotoxicity, proteomic, transcriptional, other...
Triple-negative breast cancer (TNBC) and ovarian each comprise heterogeneous tumors, for which current therapies have little clinical benefit. Novel that target eradicate tumor-initiating cells (TIC) are needed to significantly improve survival.A panel of well-annotated patient-derived xenografts (PDX) was established, surface markers enriched TIC in specific tumor subtypes were empirically determined. The TICs queried overexpressed antigens, one selected be the an antibody-drug conjugate...
Abstract Antibody–drug conjugates (ADC) represent a promising therapeutic modality for the clinical management of cancer. We sought to develop novel ADC that targets 5T4, an oncofetal antigen expressed on tumor-initiating cells (TIC), which comprise most aggressive cell population in tumor. optimized anti-5T4 (A1mcMMAF) by sulfydryl-based conjugation humanized A1 antibody tubulin inhibitor monomethylauristatin F (MMAF) via maleimidocaproyl linker. A1mcMMAF exhibited potent vivo antitumor...
Poorly differentiated tumors in non-small cell lung cancer (NSCLC) have been associated with shorter patient survival and time to recurrence following treatment. Here, we integrate multiple experimental models clinicopathologic analysis of delineate a cellular hierarchy NSCLC. We show that the oncofetal protein 5T4 is expressed on tumor-initiating cells worse clinical outcome Coexpression factors involved epithelial-to-mesenchymal transition were observed undifferentiated but not tumor...
Abstract Purpose: Linking a cytotoxic anticancer drug to an antibody that recognizes tumor-associated antigen can improve the therapeutic index of drug. We asked whether conjugate antibiotic N-acetyl γ calicheamicin dimethyl hydrazide (CalichDMH) and recognizing Lewisy (Ley) could eliminate carcinomas express Ley. Because Ley is highly expressed on colon, breast, lung, ovary, prostate, CalichDMH targeting provide treatment option for various cancers. Experimental Design: The humanized...
The oncofetal protein, 5T4, is a tumor-associated protein displayed on the cell membrane of various carcinomas. This molecule promising target for anti-tumor vaccine development and targeted therapy with staphylococcus exotoxin. potential use 5T4 as antibody-guided chemotherapy has not been demonstrated. We report oncolytic efficacy selectivity in vitro vivo immuno-conjugates calicheamicin (CM) anti-5T4 antibody, H8. CM potent cytotoxic drug that causes double strand breaks DNA. Conjugates...
Calicheamicin is a potent chemotherapeutic with low therapeutic index that requires targeting to tumor cells for its use in the clinic. To treat acute myeloid leukemia, calicheamicin has been conjugated an antibody recognizes CD33 (gemtuzumab ozogamicin). The application range of this ‘active’ strategy limited since it depends on specific antigen expression by cells. This limitation could be reduced using antigen-independent ‘passive targeting’ calicheamicin. ‘Passive relies dysfunctional...
RPHPLC of the tryptic digest lysine blocked group A streptococcal PepM49 protein (DHP‐PepM49) consistently yielded, among others, two pairs peptides which were well resolved, eluted in tandem, and had identical amino acid compositions. In each pair, earlier eluting peptide was readily amenable to sequencing yielded an amino‐terminal glutamine whereas later could not be sequenced. Mass spectral analysis revealed that these differed mass corresponding loss ammonia. These data suggested pair is...
Abstract Extra domain B splice variant of fibronectin (EDB+FN) is an extracellular matrix protein (ECM) deposited by tumor-associated fibroblasts, and associated with tumor growth, angiogenesis, invasion. We hypothesized that EDB+FN a safe abundant target for therapeutic intervention antibody–drug conjugate (ADC). describe the generation, pharmacology, mechanism action, safety profile ADC specific (EDB-ADC). broadly expressed in stroma pancreatic, non–small cell lung (NSCLC), breast,...
Abstract Antibody-drug conjugates (ADCs) enable targeted delivery of therapeutics to cancer cells and offer potential for more selective therapy. Several ADCs are demonstrating promising clinical efficacy, however due the complexity human cancer, tumors become refractory most drug treatments. We hypothesized that cultured tumor chronically treated with an ADC would acquire mechanisms resistance unique ADC-based Human breast cell lines were exposed multiple cycles anti-Her2...
The association of only certain M protein serotypes group A streptococci with acute glomerulonephritis is very well recognized. Structural information on the protein, a dimeric alpha-helical coiled-coil molecule, has come so far from three rheumatogenic serotypes, 5, 6, and 24. However, proteins nephritogenic have not been characterized. In present study, we isolated biologically active 20,000 Mr pepsin fragment type 49 (PepM49), serotype, purified it to homogeneity using DEAE-Sephadex gel...
The complete amino acid sequence of PepM49, a peptic fragment the group A streptococcal type 49 M protein, antiphagocytic cell surface molecule bacteria, is described. This retains opsonic antibody epitope native molecule. as determined by automated Edman degradations uncleaved molecule, and its tryptic chymotryptic peptides, consists total 143 residues (Mr = 17,187). nephritis-associated protein serotype, exhibits significant internal homology in sequence. However, identical repeats kind...
CMC-544 (Inotuzumab ozogamicin) is a CD22-targeted immunoconjugate of calicheamicin currently being evaluated in phase III clinical trials patients with non- Hodgkin’s B-cell lymphoma. the product collaboration between Wyeth and UCB-Celltech. has demonstrated significant activity both follicular diffuse large lymphoma who had failed multiple therapies.1,2 (Figure 1) humanized IgG4 anti-CD22 antibody (G5/44) covalently linked to N-acetyl gamma dimethyl hydrazide (CalichDMH) via an acid-labile...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTHelix formation in enzymically ligated peptides as a driving force for the synthetic reaction: example of .alpha.-globin semisynthetic reactionRajendra Prasad Roy, Kiran M. Khandke, B. N. Manjula, and A. Seetharama AcharyaCite this: Biochemistry 1992, 31, 32, 7249–7255Publication Date (Print):August 1, 1992Publication History Published online1 May 2002Published inissue 1 August...
Abstract Patient-derived xenografts (PDXs) are resected human tumors engrafted into mice and represent personalized murine ‘avatars' of those tumors. PDXs valuable tumor models for drug development since they recapitulate the complexity microenvironment more extensively than cell line (CLXs). Unlike CLXs, never passaged in vitro, therefore faithfully native biology response to therapeutics. Thus, may accurately predict clinical activity therapeutic compounds traditional CLXs. We developing a...
Abstract Triple-negative breast cancer (TNBC) and ovarian comprise heterogeneous tumors, neither targeted therapies nor traditional chemotherapies have provided consistent clinical benefit. Novel that target actively eradicate the subpopulation of tumor cells mediate drug resistance relapse could significantly improve patient survival. Tumor-initiating (TIC) are functionally defined as drive long-term growth, to therapy disease relapse. We herein identified CD324 a surface antigen able...
Abstract Antibody-drug conjugates (ADCs) enable targeted delivery of therapeutics to cancer cells and offer potential for more selective therapy. Several ADCs are demonstrating promising clinical efficacy, however due the complexity human cancer, tumors become refractory most drug treatments. We hypothesized that cultured tumor chronically treated with an ADC would acquire mechanisms resistance unique ADC-based As a model system, we used trastuzumab-maytansinoid (TM) similar T-DM1 treat cell...