Background:

Glioblastoma (GBM) is the most prevalent primary malignant brain tumor. Clinically, GBM is detected in its advanced stages with a 5-year survival rate of 10-12 months. The main goal of treatment in GBM patients is to prolong patients' life expectancy and delay disease progression. Historical changes in GBM treatment have seen the incorporation of maximal surgical resection, radiation, and chemotherapy. Recent developments focus on immunotherapy and targeted therapeutic approaches. In the early 2000s, research into the possible connection between cytomegalovirus (CMV) and glioblastoma (GBM) sparked after Initial studies detected CMV in GBM biopsies. Current research seeks to elucidate CMV's involvement in GBM and evaluate its applicability for targeted therapeutic approaches. Autologous T-cell therapy for CMV-specific targeting in glioblastoma involves the genetic modification of a patient's T-cells to recognize CMV. These modified T-cells are reintroduced to seek out and attack CMV-infected GBM cells, potentially offering a precise and innovative treatment approach. The objective of this study is to assess the effectiveness of CMV-Specific Autologous T-Cell Therapy on both progression-free survival and overall survival in patients diagnosed with Glioblastoma.

 

Materials and Methods:

A systematic search across seven electronic databases, including Medline, Cochrane, Science Direct, SCOPUS, Springerlink, EBSCOhost, and ClinicalTrials.gov, was conducted to identify relevant studies from their inception until September 2023. Screening of titles and abstracts was carried out for 888 studies, leading to the selection of 21 studies for full-text screening. Among these, five studies met the inclusion criteria for the systematic review, with three of them being included in the subsequent meta-analysis. The study adhered to the PRISMA guidelines (2020) for its methodology.

 

Results: 

In the pooled analysis comprising three included studies and a collective patient population of 66 individuals, CMV-targeted autologous T-cell therapy demonstrated a significant enhancement in overall survival for GBM patients, with a mean difference of 28.86 (95% CI; 23.51 – 34.2, P < 0.00001). Notably, the results exhibited homogeneity across the studies (I2 = 0%, P = 0.83). Moreover, data analysis showed improved progression-free survival with a mean difference of 22.36 [95% CI; 17.3 – 27.41, P <0.00001]. The results were homogenous (I2 = 0%, P = 0.49).

 

Conclusion: 

This systematic review and meta-analysis unveils the significant potential of CMV-targeted autologous T-cell therapy in enhancing the survival of Glioblastoma patients. These findings underscore the promising outcomes of CMV-targeted autologous T-cell therapy and point toward a potential paradigm shift in GBM therapy. However, it's crucial to recognize the current scarcity of clinical trials in this specialized field. We strongly urge clinicians and researchers to embark on comprehensive, well-structured clinical trials that could refine our understanding and pave the way for innovative and effective treatments in the future, offering renewed hope to GBM patients.