Clinical Responsiveness of Glioblastoma Multiforme to Chemotherapy after Vaccination

Wheeler, Christopher J.; Das, Asha; Liu, Gentao; Yu, John S.; Black, Keith L.

doi:10.1158/1078-0432.ccr-04-0497

Cited by 240 publications

(172 citation statements)

References 37 publications

(31 reference statements)

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“…In addition, Wheeler et al 13 analyzed survival and the time to disease progression in vaccinated (tumorpulsed DCs) and nonvaccinated patients with glioblastoma who received chemotherapy. Vaccinated patients who received subsequent chemotherapy exhibited significantly longer times to tumor recurrence after chemotherapy relative to their own previous recurrence times and had significantly longer postchemotherapy recurrence times and survival relative to patients who received vaccination or chemotherapy alone.…”

Section: Therapeutic Vaccines Combined With Chemotherapymentioning

confidence: 99%

A new era in anticancer peptide vaccines

Perez

Hofe

Kallinteris

et al. 2010

Cancer

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The use of synthetic peptides as vaccines aimed at the induction of therapeutic CD8-positive T-cell responses against tumor cells initially experienced great enthusiasm, mostly because of advances in vaccine technology, including design, synthesis, and delivery. However, despite impressive results in animal models, the application of such vaccines in humans has met with only limited success. The therapeutic activity of vaccine-stimulated, tumor-specific, CD8-positive T cells can be hampered through the physical burden of the tumor, tolerance mechanisms, and local factors within the tumor microenvironment. Recently, accumulating evidence has suggested that combining a peptide-based therapeutic vaccination with conventional chemotherapy can uncover the full potential of the antitumor immune response, increasing the success of immunotherapy. In addition, therapeutic vaccination in the preventive setting has been extremely effective in eliciting antitumor responses in preclinical tumor models and has demonstrated good promise clinically in patients with minimal residual disease. The rationale behind preventive vaccination is that patients with minimal tumor burden still have a fully competent immune system capable of developing robust antitumor responses. Finally, therapeutic CD8-positive T-cell peptide vaccines have been improved by coimmunization with T-helper epitopes expressed on long peptides.

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Section: Therapeutic Vaccines Combined With Chemotherapymentioning

confidence: 99%

A new era in anticancer peptide vaccines

Perez

Hofe

Kallinteris

et al. 2010

Cancer

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“…Unfortunately, this has largely not been realized in patients with glioblastoma multiforme (5). Despite a negligible incidence of metastasis, aggressive surgery, and the application of novel chemotherapeutics, patients with glioblastoma multiforme, the most common and lethal form of primary brain cancer, typically live <1 year from the time of diagnosis (6). Recurrence of tumor following surgical resection and chemotherapy is very high (>90%), and survival of these patients is usually <12 weeks (7).…”

mentioning

confidence: 99%

“…In addition, severely reduced total CD4 + counts (15) and diminished delayed type hypersensitivity (16,17) responses are hallmarks of patients with glioblastoma multiforme. Although the exact nature of T-cell lymphopenia in glioblastoma multiforme is not well understood, recent reports have suggested that mechanisms contributing to this deficiency may include dysregulation of thymic output (6), increased regulatory T-cell (T reg ) fraction (15), and tumor-induced immunosuppression (8). Severe T-cell lymphopenia, especially in the CD4 + compartment, is commonly observed in patients with glioblastoma multiforme (15).…”

mentioning

confidence: 99%

Profiling of CD4+, CD8+, and CD4+CD25+CD45RO+FoxP3+ T Cells in Patients with Malignant Glioma Reveals Differential Expression of the Immunologic Transcriptome Compared with T Cells from Healthy Volunteers

Learn¹,

Fecci²,

Schmittling³

et al. 2006

Clinical Cancer Research

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Purpose: Analyses of T-cell mRNA expression profiles in glioblastoma multiforme has not been previously reported but may help to define and characterize the immunosuppressed phenotype in patients with this type of cancer. Experimental Design: We did microarray studies that have shown significant and fundamental differences in the expression profiles of CD4 + and CD8 + T cells and immunosuppressive CD4 + CD25 + CD45RO + FoxP3 + regulatory T cells (T reg ) from normal healthy volunteers compared with patients with newly diagnosed glioblastoma multiforme. For these investigations, we isolated total RNA from enriched CD4 + and CD8 + Tcell or T reg cell populations from age-matched individuals and did microarray analyses. Results: ANOVA and principal components analysis show that the various T cell compartments exhibit consistently similar mRNA expression profiles among individuals within either healthy or brain tumor groups but reflect significant differences between these groups. Compared with healthy volunteers, CD4 + and CD8 + T cells from patients with glioblastoma multiforme display coordinate down-regulation of genes involved in T cell receptor ligation, activation, and intracellular signaling. In contrast,T regs from patients with glioblastoma multiforme exhibit increased levels of transcripts involved in inhibiting host immunity. Conclusion: Our findings support the notion that key differences between expression profiles in T-cell populations from patients with glioblastoma multiforme results from differential expression of the immunologic transcriptome, such that a limited number of genes are principally important in producing the dysregulated T-cell phenotype.

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“…But a study conducted in 2004 (Wheeler et al, 2004) showed that vaccination or chemotherapy alone could not elicit significant tumor regressions whereas chemotherapy following DC vaccination significantly improved the mean survival of patients (p=0.04). Although most of our patients did not show any objective clinical response, one of the patients in arm III (patient 3) with a prominent lung metastasis, showed an excellent response to cisplatin chemotherapy given nearly a year after the third DC vaccine dose.…”

Section: Discussionmentioning

confidence: 99%

Development and Clinical Evaluation of Dendritic Cell Vaccines for HPV Related Cervical Cancer - a Feasibility Study

Ramanathan¹,

Ganesarajah²,

Raghanvan³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Human papillomavirus infection (HPV) and HPV related immune perturbation play important roles in the development of cervical cancer. Since mature dendritic cells (DCs) are potent antigen-presenting cells (APC), they could be primed by HPV antigens against cervical cancers. In this study we were able to generate, maintain and characterize, both phenotypically and functionally, patient specific dendritic cells in vitro. A randomized Phase I trial with three arms -saline control (arm I), unprimed mature DC (arm II) and autologous tumor lysate primed mature DC (arm III) and fourteen patients was conducted. According to WHO criteria, grade 0 or grade one toxicity was observed in three patients. One patient who received tumor lysate primed dendritic cells and later cis-platin chemotherapy showed a complete clinical response of her large metastatic disease and remained disease free for more than 72 months. Our findings indicate that DC vaccines hold promise as adjuvant sfor cervical cancer treatment and further studies to improve their efficacy need to be conducted.

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Clinical Responsiveness of Glioblastoma Multiforme to Chemotherapy after Vaccination

Cited by 240 publications

References 37 publications

A new era in anticancer peptide vaccines

A new era in anticancer peptide vaccines

Profiling of CD4+, CD8+, and CD4+CD25+CD45RO+FoxP3+ T Cells in Patients with Malignant Glioma Reveals Differential Expression of the Immunologic Transcriptome Compared with T Cells from Healthy Volunteers

Development and Clinical Evaluation of Dendritic Cell Vaccines for HPV Related Cervical Cancer - a Feasibility Study

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