A comprehensive update to Dendritic Cell therapy for glioma: a systematic review and meta-analysis

ABSTRACT

Background

Gliomas are major challenges of neuro-oncology due to high mortality. Clinical applications of dendritic cells (DCs) have yielded promising results in the clinical trial pipelines over decades.

Research design

In this systematic review, we critically discuss the current status, future perspective, and challenges of DC therapy for gliomas . and summarize the study population, blinding, comparators, dosage, treatment regimens, efficacy, and safety issues of the clinical trials published on DC therapy for gliomas and also report the results of our meta-analysis on safety and immunological efficacy of DC therapy for gliomas.

Results

The results of our meta-analysis indicated that the most frequent grade I/II adverse event (AE) reported in phase I or phase I/II trials was fatigue (∼16% and 24%). Moreover, in phase II trials, fatigue and cytopenia were the most common AEs (∼9% and 14%). Meanwhile, Grade III/IV AEs were rare . Moreover, our meta-analysis indicated ∼64% CD8+ T cells infiltration into tumor site after DC therapy and also ∼45% IFNγ increase.

Conclusions

DC therapy could serve as a potential immunotherapy for gliomas; however, limitations exist to draw certain conclusions due to diversity of the criteria applied to assess clinical response and limited data on patients’ survival.

KEYWORDS:

• Glioma
• Immunotherapy
• dendritic cells
• efficacy
• safety
• meta-analysis

Article highlights

• The results of our meta-analysis indicated that DC therapy is safe and well-tolerated with the most probable adverse events being fatigue and has relatively lower adverse events compared to the current standard of care chemotherapy or radiation therapy protocols.

• The results of our meta-analysis indicated that INFγ increase as an experimental measure for increased cytolytic activity (CTL) activity was reported in ∼45% of the 222 patients undergoing DC therapy. Moreover, the development of delayed-type hypersensitivity (DTH) representative of local cellular immune responses was seen in ∼48% of 97 glioma patients and CD8+ T cells infiltration was significantly increased in ∼64% of 22 patients who experienced recurrence after DC therapy.

• Glioma DC therapy has yielded acceptable clinical response rates and hence DC-based pharmaceutics may serve as potent adjuvants to the current standard of care treatments for glioma comprising radiation therapy, chemotherapy, and immunotherapeutics (e.g. anti-angiogenic monoclonal antibodies).

• A rising concern is to establish novel strategies to increase the clinical efficacy of DC therapy, improve antigen selection strategies, optimize the maturation process, and provide novel strategies for adequate DC delivery.

• Dexosomes as next-generation cell-free nanotherapeutics could serve as potential alternatives to DC therapy that may induce more potent immunostimulatory responses due to a dense accumulation of surface MHC I/II-antigen complexes on their surface with minimal AEs.

Author contributions

MN, DA, and MA developed the idea, supervised the study, and participated in writing the manuscript. PS and PM performed the meta-analysis, developed the idea, and wrote the manuscript.

Data availability

All data presented in the current work is available in the text and supplementary materials and can also be obtained from the authors upon request.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Ethical approval

This study was approved by the ethics committee of NIMAD institute (IR.NIMAD.REC.1398.047).

Reviewer disclosures

A reviewer on this manuscript has disclosed that they have filed multiple patent applications on novel mRNA vaccine technologies some that have exclusive option to license by iOncologi, inc.

Additional information

Funding

This paper was not funded.