Compositions comprising Anti-cd38 antibodies and carfilzomib
a technology which is applied in the field of anti-cd38 antibodies and carfilzomib, and cancer treatments, and can solve the problems of patients succumbing to their illness and unable to resis
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example 1
Effect of the Administration of Both Anti-CD38 Antibody and Carfilzomib in a Mice Model of MM
[0074]These studies under this Example were done under approval of the UCSF IACUC.
[0075]The subcutaneous multiple myeloma (MM) xenograft mouse models were established using NCI-H929 or RPMI-8226 cell lines. Specifically, 5-6 week old female Balb / c Scid mice were obtained from Jackson Lab. Mice were housed for 7-10 days prior to implantation. Mice were housed in a dedicated room in the UCSF Mt Zion Animal Barrier Facility. NCI-H929 and RPMI-8226 cells were obtained from the German Collection of Microorganisms and Cell Cultures, DSMZ, (Deutsche Sammlung von Mikroorganismen and Zellkulturen), and grown in sterile suspension culture in T225 flasks as follows: NCI-H929: RPMI1640+20% FBS+4 mM L-glutamine+1 mM sodium pyruvate+50 μM mercaptoethanol. RPMI-8226: RPMI1640+10% FBS+4 mM L-glutamine.
[0076]At the time of implantation, mice were shaved on the right flank and shoulder region and anesthetized...
example 2
Effect of the Administration of Both Anti-CD38 Antibody and Carfilzomib in Humans
[0085]A clinical study for evaluating the effects of a treatment with hu38SB19 combined with carfilzomib in patients with relapsed or refractory multiple myeloma may be performed as described below.
[0086]The goals of the study may include:[0087]To determine the efficacy and the maximum tolerated dose;[0088]To evaluate the safety, including immunogenicity, of hu38SB19 in combination with carfilzomib in relapse or refractory multiple myeloma. The severity, frequency and incidence of all toxicities is assessed;[0089]To evaluate the pharmacokinetics (PK) of hu38SB19 when administered in combination with carfilzomib and the PK of carfilzomib in combination with hu38SB19, and optionally dexamethasone.[0090]To assess the relationship between clinical (adverse event and / or tumor response) effects and pharmacologic parameters (PK / pharmacodynamics), and / or biologic (correlative laboratory) results;[0091]Estimate ...
example 3
Efficacy of Anti-CD38 Antibody in In Vivo Tumor Models of Multiple Myeloma as a Single-Agent or in Combination with and Carfilzomib
A. Materials and Methods
[0102]CD38 Density: CD38 density was determined using anti-CD38-PE Quantibrite (BD Biosciences; Cat.342371) per the manufacturer's recommended protocols.
[0103]Reagents & Compounds: hu38SB19 was provided by Sanofi Oncology in solution at 5 mg / ml and stored at 4° C. hu38SB19 was diluted into sterile saline in preparation for dosing and used within 10 days of dilution. hu38SB19 was administered twice weekly×2 wk IV. Carfilzomib (PR-171) was obtained from Chemie Tek (CT-CARF 98). Carfilzomib was formulated in an aqueous solution of 10% (w / v) sulfobutylether-h-cyclodextrin (Cydex) and 10 mmol / L sodium citrate (pH 3.5), 2 mg / ml stock prepared and frozen at −80° C., diluted daily with vehicle before injection. Carfilzomib was administered weekly qd×2×3 wk (iv).
[0104]Test Animals: 5-6 week old female Balb / c Scid mice were obtained from Ja...
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