Synergistic Antitumor Efficacy of A Modified Survivin Peptide Vaccine and Temozolomide in A Murine Model of Cerebral Glioma — ASN Events

Synergistic Antitumor Efficacy of A Modified Survivin Peptide Vaccine and Temozolomide in A Murine Model of Cerebral Glioma (#22)

Zhengwen He 1 , Michael J. Ciesielski 2 , Cheryl Frank 2 , Shousong Cao 2 , Robert A. Fenstermaker 2
  1. Hunan Cancer Hospital, Changsha, China
  2. Department of Neurosurgery, Roswell Park Cancer Institute, Buffalo, NY 14263, USA

Background:  Since Temozolomide (TMZ) is the most often used chemotherapy for the treatment of glioma, we studied the efficacy of the combination of TMZ and vaccine(sur-vax ), in order to make the scientific rational for clinical trial.    

Methods: GL261 murine glioma cells were used with MTT method for the in vitro cytotoxicity studies. For the in vivo studis, mice models of brain tumor and subcutaneous (s.c) implanted tumor were used with control, TMZ alone, Vax alone, and TMZ + Vax, respectively. Survival time and tumor volume were analysed for antitumor efficacy of brain medol and  s c. model,  respectively. Immunohistochemistry of CD4+T cells,  CD8+ T cells,  Tregs were performed to investigate the local Immune responese.

Results: The combination of Vax and TMZ is safe with no significantly side effects were observed in the treated mice. The mice treated with TMZ alone has a 20% survival benefit comparing with the control group,  The mice treated with Vax survived significantly longer than the TMZ group, and the mice treated with the combination of TMZ and Vax live ever longer than that of the group of Vax treatment .  Similar result is achieved with subcutaneous (s.c) tumor model Showed compared to the brain tumor model. Immunohistochemistry analysis of the brain sections showed that CD4+ T cells expression was observed in all four groups,Vax group slightly increased  the experession comparing with the control group, but the groups of  TMZ alone and the TMZ + Vax significantly increased the experssion. While    CD8+ T cells expression in  both sur-vax alone and sur-vax +TMZ groups are increased . For Tregs, TMZ and TMZ+sur-vax groups could significantly decrease the expression of tregs yet sur-vax not.  

 Conclusions: The findings suggest that the combination may be safely and increase antitumor efficacy to  the patient with malignant glioma in clinical trials.  

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