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22 results on '"Trisal, Preeti"'

3. Single-Cell Multi-Omics Reveals Distinct Paths to Survival of Admixed BTKC481 Mutant Vs. Wild-Type Cells in Clinically Progressing Chronic Lymphocytic Leukemia

Author

Lipsky, Andrew, Luan, Danny, Chen, Shirley, Chaligne, Ronan, Dusaj, Neville, Bhavsar, Erica B, Ang, Chelston, Nam, Anna S, Gaiti, Federico, Chamely, Paulina, Omans, Nathaniel D., Trisal, Preeti, Gandhi, Anita K, Kim, Kyu-Tae, Schulman, Rafael, Schiffman, Joshua S., Izzo, Franco, Mullokandov, Gregory, Underbayev, Chingiz, Wiestner, Adrian, Allan, John N., Furman, Richard R., and Landau, Dan A.

Published
2020
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5. Combination lenalidomide‐rituximab immunotherapy activates anti‐tumour immunity and induces tumour cell death by complementary mechanisms of action in follicular lymphoma

Author

Chiu, Hsiling, primary, Trisal, Preeti, additional, Bjorklund, Chad, additional, Carrancio, Soraya, additional, Toraño, Estela G., additional, Guarinos, Carla, additional, Papazoglou, Despoina, additional, Hagner, Patrick R., additional, Beldi‐Ferchiou, Asma, additional, Tarte, Karin, additional, Delfau‐Larue, Marie‐Hélène, additional, Morschhauser, Franck, additional, Ramsay, Alan G., additional, and Gandhi, Anita K., additional

Published
2019
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8. Single-Cell Multi-Omics Reveals Distinct Paths to Survival of Admixed BTKC481Mutant Vs. Wild-Type Cells in Clinically Progressing Chronic Lymphocytic Leukemia

Author

Lipsky, Andrew, Luan, Danny, Chen, Shirley, Chaligne, Ronan, Dusaj, Neville, Bhavsar, Erica B, Ang, Chelston, Nam, Anna S, Gaiti, Federico, Chamely, Paulina, Omans, Nathaniel D., Trisal, Preeti, Gandhi, Anita K, Kim, Kyu-Tae, Schulman, Rafael, Schiffman, Joshua S., Izzo, Franco, Mullokandov, Gregory, Underbayev, Chingiz, Wiestner, Adrian, Allan, John N., Furman, Richard R., and Landau, Dan A.

Abstract

Mutations in the kinase binding domain of BTK at position C481 are associated with resistance to BTK inhibitor (BTKi) therapy in chronic lymphocytic leukemia (CLL). Nearly half of patients manifesting clinical progression with these alterations exhibit a subclonal burden of resistance. Intriguingly, measured BTKC481variant allelic fractions (VAF) are commonly lower than 10% [Ahn et al,Blood 2017]. This raises the important question of how BTKC481-mutated (MUT) and wildtype (WT) cells differ in their response to therapeutic challenge, and how low-burden MUT subclones facilitate escape from therapy.

Published
2020
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13. Abstract 4402: The anti-tumor effects of two novel multivalent/multifunctional agents derived from hR1, a humanized anti-insulin-like growth factor receptor-I monoclonal antibody, are enhanced in renal cell carcinoma and synergistic with an mTOR inhibitor

Author

Cardillo, Thomas M., primary, Nair, Anju, additional, Zalath, Maria, additional, Arrojo, Roberto, additional, Trisal, Preeti, additional, Rossi, Edmund A., additional, Goldenberg, David M., additional, and Chang, Chien-Hsing, additional

Published
2012
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19. Improving the Therapeutic Index in Cancer Therapy by Using Antibody–Drug Conjugates Designed with a Moderately Cytotoxic Drug

Author

Govindan, Serengulam V., Cardillo, Thomas M., Rossi, Edmund A., Trisal, Preeti, McBride, William J., Sharkey, Robert M., and Goldenberg, David M.

Abstract

The antibody–drug conjugate (ADC), IMMU-130, of the moderately cytotoxic topoisomerase I inhibitor, SN-38, and the CEACAM5-targeted humanized antibody (mAb), labetuzumab, was evaluated in model systems of human colon carcinoma and in phase I clinical trials of heavily pretreated patients with metastatic colorectal cancer. The conjugate, designed with a near-homogeneous drug substitution of 7–8 SN-38/mAb and with a linker that released 50% of the drug in ∼20 h, showed significant antitumor effects compared to a nontargeted ADC in human tumor xenografts, which could be augmented in combination with bevacizumab. The advantage of fractionated dosing was demonstrated, with potential implications for the clinical dosing schedule. Biodistribution comparing IMMU-130 with labetuzumab showed that the conjugate cleared somewhat faster from the blood, but this did not affect tumor uptake and retention. The use of an ultrastable linker in the conjugate design abrogated antitumor effects. A tolerability study in rabbits showed a high safety margin, with no-observed-adverse-effect level (NOAEL) corresponding to a cumulative human-equivalent protein dose of 40–60 mg/kg. The preclinical findings appear to be corroborated in two phase I clinical trials, with high tolerability and evidence of antitumor activity, including objective responses. The impact of the ADC design on the utility of IMMU-130, tailored to a poorly internalizing target, is discussed.

Published
2015
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20. Evaluation of a Novel Hexavalent Humanized Anti-IGF-1R Antibody and Its Bivalent Parental IgG in Diverse Cancer Cell Lines.

Author

Chien-Hsing Chang, Yang Wang, Trisal, Preeti, Rongxiu Li, Rossi, Diane L., Nair, Anju, Gupta, Pankaj, Losman, Michele, Cardillo, Thomas M., Rossi, Edmund A., Goldenberg, David M., and Zhaozhong Han

Subjects
MONOCLONAL antibodies, GROWTH factors, CELL proliferation, CANCER cells, TUMOR growth, LABORATORY rats
Abstract

A major mechanism of monoclonal antibodies that selectively target the insulin-like growth factor type 1 receptor (IGF-1R) to inhibit tumor growth is by downregulating the receptor, regardless whether they are capable (antagonistic) or incapable (agonistic) of blocking the binding of cognate ligands. We have developed and characterized a novel agonistic anti-IGF-1R humanized antibody, hR1, and used the Dock-and-Lock (DNL) method to construct Hex-hR1, the first multivalent antibody comprising 6 functional Fabs of hR1, with the aim of enhancing potency of hR1. Based on cross-blocking experiments, hR1 recognizes a region of cysteine-rich domain on the α-subunit, different from the epitopes mapped for existing anti-IGF-1R antibodies, yet hR1 is similar to other anti-IGF-1R antibodies in downregulating IGF-1R and inhibiting proliferation, colony formation, or invasion of selected cancer cell lines in vitro, as well as suppressing growth of the RH-30 rhabdomyosarcoma xenograft in nude mice when combined with the mTOR inhibitor, rapamycin. Hex-hR1 and hR1 are generally comparable in their bioactivities under the in-intro and in-vivo conditions investigated. Nevertheless, in selective experiments involving a direct comparison of potency, Hex-hR1 demonstrated a stronger effect on inhibiting cell proliferation stimulated by IGF-1 and could effectively downregulate IGF-1R at a concentration as low as 20 pM. [ABSTRACT FROM AUTHOR]

Published
2012
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22. IMPACT OF NONIONIZABLE GLYCOL SOLUBILIZERS EXHIBITING DIFFERENT SURFACE ACTIVITIES ON INTESTINAL MEMBRANE PERMEABILITY

Author

TRISAL, PREETI

Subjects
Health Sciences, Pharmacy, solubility, excipients, paracellular, transcellular, surfactants, hydrotropes
Abstract

Oral delivery of hydrophobic drugs exhibiting poor aquous solubility represents a difficult challenge in modern drug development. Self-emulsifying drug delivery systems (SEDDS) have effectively been used to increase oral bioavailability of such compounds. Recent studies indicated that surface-active excipients incorporated into SEDDS not only affect drug solubility but may also interfere with crucial barrier properties of the intestinal mucosa limiting transepithelial transport. Nevertheless, relevant structure-function relationships have not yet been established. In this study we determined physicochemical properties of diethyleneglycol monoethyl ether (DGME, Transcutol P®) and caprylocaproyl macrogolglycerides (CCMG, Labrasol®), two excipients commonly used in SEDDS, and compared their effect on intestinal membrane permeability using the in vitro Caco-2 cell culture model. Concentration-dependent surface activity, microstructure, and phase behavior in the ternary monoolein/water/solubilizer system were used to assess physicochemical properties of DGME and CCMG, respectively. Solubilizer-induced changes in physical barrier properties of Caco-2 cell monolayers were assessed using transepithelial electrical resistance and membrane fluidity measurements. Effects on membrane permeability were determined by quantifying transepithelial transport of marker solutes that permeate the epithelial barrier via different pathways. Finally, cytotoxicity profiles of the solubilizers were estimated using MTT and LDH assays. The results from these studies suggest that both excipients exhibit surface-active properties and undergo self-aggregation beyond a specific solution concentration. For DGME, however, this limiting concentration where self-aggregation occurs is significantly greater than for CCMG. Furthermore, inclusion of this glycol ether into the binary monoolein/water system results in a broad region of isotropic liquid. This implies that DGME exhibits more hydrotrope-like properties, whereas the behavior of CCMG follows more that of a classical surfactant. Subsequent studies using the Caco-2 cell culture model demonstrated that the hydrotrope-like DGME exhibits a superior gastrointestinal safety profile over the surfactant-like CCMG. Both solubilizers were effective as permeation enhancers for solutes traversing the intestinal mucosa via passive transcellular and paracellular diffusion. In addition, inclusion of CCMG and DGME into the transport buffer inhibited functional activity of intestinal P-glycoprotein. However, it appears that DGME is less potent as permeation enhancer than CCMG, because it always required greater concentrations of the hydrotrope-like excipient to induce significant changes in intestinal permeability. For practical applications, this implies that surfactant-like excipients may serve more effectively in a dual role as solubilizer and permeation enhancer in oral SEDDS than solubilizers with hydrotrope-like properties.

Published
2005

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