Abstract 2902: Obinutuzumab (GA101) significantly increases overall survival against CD20+ rituximab-sensitive and -resistant Burkitt (BL) and acute lymphoblastic leukemia (B-ALL): potential targeted therapy in patients with high risk BL and pre-B-ALL

Abstract

Background: Patients who relapse with CD20+ B-NHL and B cell Acute lymphoblastic leukemia (B-LL) have a dismal prognosis, which is often associated with chemotherapy resistance and may require alternative therapeutic strategies (Cairo et al. JCO, 2012, Barth/Cairo et al. BJH, 2013). Rituximab (RTX) in combination with FAB 96 chemotherapy is a safe and well-tolerated and is associated with > 90% EFS in children with newly diagnosed and advanced mature B-Cell NHL (Goldman/Cairo et al. Leukemia, 2013). Resistance to RTX, however, may predispose patients with CD20+ B-LL to an increase risk of relapse and/or disease progression (Barth/Cairo et al. BJH, 2012; Tsai et al. Cl. Can. Res, 2012). Obinutuzumab, a novel type II glycoengineered CD20 antibody, mediates enhanced cell death and ADCC vs. RTX (Bologna L et al. JI, 2012), and was recently approved by FDA for first line treatment of CLL in combination with chlorambucil. Objective: To evaluate anti-tumor activity of obinutuzumab vs RTX against RTX resistant and sensitive BL and pre-B-ALL in xenografted NSG mice. Methods: Raji (CD20+) and Loucy (T-ALL, CD20-), (ATCC, Manhass, VA), U698-M (CD20+, DSMZ, Germany) and Raji-4RH (provided by M. Barth, Roswell Park Cancer Institute) were cultured in RPMI with 10% FBS. The lentiviral construct, pSico PolII-eGFP-Luc2, was transfected into Raji, Raji 4RH (RTX resistant), U698M and Loucy. Six to 8 week old female NSG (NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ), mice were bred in house under pathogen free conditions, NSG mice were divided into 5 groups: PBS only (control), isotype control (IgG), obinutuzumab 10 mg/kg (generously supplied by Christian Klein, PhD (Roche)), obinutuzumab (30 mg/kg), and rituximab (30 mg/kg). Mice were xenografted with intravenous injections of Luc+ Raji, Raji4RH, U698M and Loucy cells at 5x106 tumor cells/mouse. 6-8 days after tumor cell injection, mice were then injected every 7 days with the respective therapy for 8 weeks. Mice were closely monitored for tumor burden and survival for up to 12 weeks ( approx. 80 days) via bioluminescent imaging (BLI) using the IVIS Spectrum system. Results: We demonstrated that obinutuzumab was significantly more effective than RTX when administered at the same doses in BL (RTX resistant/sensitive) and pre-B-ALL xenografts. Overall survival in mice receiving 30 mg/kg of obinutuzumab was significantly increased when compared to mice receiving 30 mg/kg of RTX in BL; Raji (p=0.0002), Raji4RH (p=0.01) and U698-M (p=0.001), respectively. Conclusion: These preliminary studies demonstrate that RTX sensitive/resistant BL and pre-B-ALL xenografted mice display significantly increased survival when given 30 mg/kg of obinutuzumab and decreased tumor burden in BL and Pre-B-ALL xenografts compared to equal dose of RTX. Citation Format: Aradhana A. Tiwari, Janet Ayello, Carmella van de Ven, Matthew J. Barth, Mitchell S. Cairo. Obinutuzumab (GA101) significantly increases overall survival against CD20+ rituximab-sensitive and -resistant Burkitt (BL) and acute lymphoblastic leukemia (B-ALL): potential targeted therapy in patients with high risk BL and pre-B-ALL. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2902. doi:10.1158/1538-7445.AM2014-2902

Dental Caries, Etiology, and Remedy through Natural Resources

“…In developing countries the herbal medicines are important sources of products in order to treat different infectious diseases and also to overcome the problems related with the available antimicrobial agents. Herbal remedies are getting popularity as they provide safe alternatives for treating various types of cancers [82][83][84][85]. These remedies are gaining interest because of their multidimensional health benefits like they are even used in different alternative treatments like acupuncture and massage therapy and by various traditional practitioners.…”

“…The medicinal uses of the plants range from administration of leaves, stem, barks, seeds, and roots to using of the decoction from different plants [86]. There has been an increase in the demand of different herbal products in the last few decades and even in countries like United States, herbal remedies are in use in the form of different dietary supplements [84,87,88].…”

“…In developing countries the herbal medicines are proving to be an important source of products in order to treat different infectious diseases and also to overcome the problems related with the available antimicrobial agents. Herbal remedies are also getting popularity for treating various types of cancers as they provide safe alternative [82][83][84][85]. Dental Caries, Etiology, and Remedy through Natural Resources http://dx.doi.org/10.5772/intechopen.75937…”