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Espaço de publicação e discussão sobre oncologia. GBM IMMUNOTHERAPY ONCO-VIRUS ONCOLOGY CANCER CHEMOTHERAPY RADIOTHERAPY



Terça-feira, 23.06.15

Phase I study of combination of antitumor immunotherapy targeted against cytomegalovirus (CMV) plus regulatory T-cell inhibition in patients with newly diagnosed glioblastoma multiforme (GBM).

Phase I study of combination of antitumor immunotherapy targeted against cytomegalovirus (CMV) plus regulatory T-cell inhibition in patients with newly diagnosed glioblastoma multiforme (GBM).

 

Category: 
Central Nervous System Tumors
Session Type and Session Title: 
This abstract will not be presented at the 2015 ASCO Annual Meeting but has been published in conjunction with the meeting.
Abstract Number: 

e13030

Citation: 
J Clin Oncol 33, 2015 (suppl; abstr e13030)
Author(s): 
Gordana Vlahovic, Gerald E. Archer, Denise Lally-Goss, Elizabeth Reap, Annick Desjardins, Katherine B. Peters, Dina Randazzo, Patrick Healy, James Emmett Herndon, Allan H. Friedman, Henry S. Friedman, Darell D. Bigner, John H. Sampson; Duke University Medical Center, Durham, NC

Abstract Disclosures

Abstract: 

Background: The inherent biologic specificity of immunotherapy offers the prospect of targeting neoplastic cells more precisely. Dendritic cells (DCs) are endowed with an extraordinary ability to activate CD4+ and CD8+ T-cells, and DCs loaded with antigens derived from tumor cells (CMV pp65-LAMP mRNA) have the potential to induce potent antitumor immunity. Furthermore, regulatory T-cells (TRegs) which induce a state of reversible immunosuppression in MG and can be functionally inactivated with anti-CD25 antibody (Ab), while dramatically enhance vaccine-induced immune responses. Our pilot group of 7 pts that received DC CMV vaccine with one dose of anti-CD25 Ab had median progression free survival (PFS) and overall survival (OS) of 23.5 months and 30.3 months respectively. There were no adverse events associated with the vaccine or anti-CD25 Ab therapy. Methods:Eligible are gross totally resected pts with newly diagnosed GBM. Pts undergo leukapheresis followed by standard of care radiation/temozolomide (XRT/TMZ) therapy. After completion of XRT/TMZ, up to 12 cycles of TMZ is administered. On Day 21 of the 1st cycle of post-XRT TMZ Vaccine # 1 is administered. Vaccines #2-3 are given biweekly following vaccine #1. Anti-CD25 Ab (basiliximab) is given twice, one week before vaccines 1 and 2. In this dose escalation study two dose levels are examined: 20 or 40 mg. An additional vaccine is given with each cycle of TMZ to a total of 8. Pts were followed with serial MRIs until disease progression. Multiple time-point immuno-monitoring by kinetics of number of TRegs and pp65 specific T cells by INFγ ELISPOT is performed for each pt. Results: 21 pts are enrolled to Phase I and to date 8 pts (7 males) have received both administrations of basiliximab and are evaluable for the determination of maximum tolerated dose. 4 pts were screen failures. No DLT or adverse events attributable to treatment are observed thus far. Conclusions: Treatment with XRT/TMZ, DC vaccine and basiliximab was well tolerated. Clinical trial information: NCT00626483

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por cyto às 17:00



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