Heat shock protein peptide complex-96 vaccination for newly diagnosed glioblastoma: a phase I, single-arm trial

Ji, Nan; Zhang, Yang; Liu, Yunpeng; Xie, Jian; Wang, Yi; Hao, Shuyu; Gao, Zhixian

doi:10.1172/jci.insight.99145

Cited by 59 publications

(71 citation statements)

References 30 publications

(45 reference statements)

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“…These findings corroborate the clinical efficacy of HSPCC-96 vaccination for treating newly diagnosed GBM as described in our previous study. 3 The clinical outcomes in these vaccinated patients notwithstanding were highly variable, such that OS ranged from 7.5 to 68.2 months. Thus, it remains critical to identify patients who will show a long-term survival benefit from HSPPC-96 vaccination.…”

Section: Updated Survival Analysis Of the Hsppc-96 Vaccinated Gbm Cohortmentioning

confidence: 98%

“…We continued our follow-up with all survivors approximately 1 y after our previous study. 3 Of the 20 vaccinated patients (19 of which had complete follow-up), 6 patients were alive with 2 of these progression-free until the last follow-up date of 15 April 2019 ( Figure 1(a,b)). After a median follow-up of 58.9 months, progression-free survival (PFS) was 20% (4/20) and overall survival (OS) was 40% (8/20) at 3 y for all vaccinated patients.…”

Section: Updated Survival Analysis Of the Hsppc-96 Vaccinated Gbm Cohortmentioning

confidence: 99%

“…This clinical trial revealed a high tolerance to treatment and promising clinical efficacy in a cohort of 20 patients. 3 Despite these encouraging results, clinical outcomes were highly variable, as reflected by the wide time range of patient survival from 7.5 to 51.0 months. 3 We also observed significantly improved outcomes in patients with a tumor-specific immune response (TSIR) post-vaccination over the median level of all included patients.…”

Section: Introductionmentioning

confidence: 99%

“…3 Despite these encouraging results, clinical outcomes were highly variable, as reflected by the wide time range of patient survival from 7.5 to 51.0 months. 3 We also observed significantly improved outcomes in patients with a tumor-specific immune response (TSIR) post-vaccination over the median level of all included patients. These patients appeared to achieve a durable survival with an average overall survival longer than 41.5 months.…”

Section: Introductionmentioning

confidence: 99%

“…These patients appeared to achieve a durable survival with an average overall survival longer than 41.5 months. 3 Since HSPPC-96 immunotherapy is costly and time-consuming, it is beneficial to select potential durable responders prior to vaccination. However, the presence of a TSIR before vaccination was unable to predict a survival benefit.…”

Section: Introductionmentioning

confidence: 99%

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T cell receptor repertoire as a prognosis marker for heat shock protein peptide complex-96 vaccine trial against newly diagnosed glioblastoma

Zhang

Mudgal²,

Wang

et al. 2020

OncoImmunology

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Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor in adults with a dismal prognosis. We previously reported that vaccination with heat shock protein peptide complex-96 (HSPPC-96) improves survival in patients with newly diagnosed GBM (NCT02122822). Especially for patients with a strong antitumor immune response after vaccination, a durable survival benefit can be achieved. Here, we conducted T cell receptor (TCR) sequencing to retrospectively examine the TCR repertoires of tumor-infiltrating lymphocytes in long-term survivors (LTS) and short-term survivors (STS). We found that LTS exhibit lower TCR repertoire diversity compared with STS, indicating the prevalence of dominant TCR clones in LTS tumors. Accordingly, the LTS group showed increased inter-patient similarity, especially among high-frequency TCR clones, implying some of these dominant clones are shared among LTS. Indeed, we discovered four TCR clones significantly enriched in the LTS group: the presence of these clones has predictive value for stratifying patients prior to vaccination. Together, these findings uncover a group of preexisting TCR clones shared in LTS that can be utilized as candidate biomarkers to select GBM patients most likely to durably respond to HSPPC-96 treatment.

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Section: Updated Survival Analysis Of the Hsppc-96 Vaccinated Gbm Cohortmentioning

confidence: 98%

Section: Updated Survival Analysis Of the Hsppc-96 Vaccinated Gbm Cohortmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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T cell receptor repertoire as a prognosis marker for heat shock protein peptide complex-96 vaccine trial against newly diagnosed glioblastoma

Zhang

Mudgal²,

Wang

et al. 2020

OncoImmunology

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Immunotherapy: Advancing glioblastoma treatment—A narrative review of scientific studies

Tiwari,

Han

2023

Cancer Reports

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BackgroundGlioblastoma (GB) is an aggressive and deadly brain tumor with a poor prognosis despite the current standard of care, including surgery, radiation, and chemotherapy.Recent FindingsIn recent years, there has been increasing interest in the potential of immunotherapies, seen to be effective in treating other cancers, in the treatment of GB. This comprehensive review presents an in‐depth analysis of the remarkable progress of immunotherapy in GB treatment, focusing on human clinical studies. It also analyzes the current findings, challenges, and limitations that underscore the transformative potential of immunotherapy in managing GB. Of particular significance, it delves into the intriguing interaction of the human microbiome with immunotherapy as a novel avenue for enhancing treatment outcomes of GB.ConclusionThis study sheds light on the complex GB therapy landscape and the cutting‐edge strategies that show promise for enhancing patient prognosis.

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Emerging Nano‐Immunotherapeutic Approaches to Glioma

et al. 2023

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Glioma is a highly invasive and frequently occurring type of brain malignancy in the central nervous system. The prognosis is often poor for glioma patients, despite the substantial advances in diagnosis and therapeutic approaches. The breakthrough discoveries in oncoimmunology have led to innovative and efficacious immunotherapeutic strategies to treat or even cure cancer patients; however, the efficacy of immunotherapy to glioma is disappointing. The unsatisfied outcomes can be explained by local immune resistance, blood–brain barrier (BBB), spatially heterogenous and immunologically specialized glioma microenvironment, etc. The emergence of nanoengineered immunotherapeutics transforms the modalities in glioma immunotherapy under preclinical and clinical settings. Nanotechnology aids the immunotherapeutics crossing the BBB and flicks the switch of immunity locally and systematically for enhanced tumor‐infiltrating effector immune cells against glioma. Herein, the advancement of knowledge in healthy brain immunology and glioma‐associated local and systemic immunosuppression is summarized and highlighted. The clinical development of immunotherapeutic approaches is discussed, such as therapeutic glioma vaccines, dendritic cell vaccines, immune checkpoint blockade, adoptive cell therapy, and new immunotargets. Herein, nanotechnology‐enabled glioma immunotherapy in preclinical and clinical studies is clarified and perspectives on future possibilities of advancing nanoengineered immunotherapeutics to clinical reality for glioma treatment are provided.

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Heat shock protein peptide complex-96 vaccination for newly diagnosed glioblastoma: a phase I, single-arm trial

Cited by 59 publications

References 30 publications

T cell receptor repertoire as a prognosis marker for heat shock protein peptide complex-96 vaccine trial against newly diagnosed glioblastoma

T cell receptor repertoire as a prognosis marker for heat shock protein peptide complex-96 vaccine trial against newly diagnosed glioblastoma

Immunotherapy: Advancing glioblastoma treatment—A narrative review of scientific studies

Emerging Nano‐Immunotherapeutic Approaches to Glioma

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