A phase I study of the WT2725 dosing emulsion in patients with advanced malignancies

Fu, Siqing; Piccioni, David; Liu, Hongtao; Lukas, Rimas V.; Kesari, Santosh; Aregawi, Dawit; Hong, David S.; Yamaguchi, Kenichiro; Whicher, Kate; Zhang, Yi; Chen, Yu-Luan; Poola, Nagaraju; Eddy, John; Blum, David

doi:10.1038/s41598-021-01707-3

Cited by 8 publications

(4 citation statements)

References 48 publications

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“…breast cancer [70] NCT02293707 (phase 2) GX301 four immunogenic peptides from human telomerase and two complementary adjuvants prostate cancer [71] NCT01621542 (phase 1) WT2725 Wilms' tumor gene 1 (WT1)-derived-oligopeptide vaccine glioblastoma [72] NCT03199872 (phase 1/2) RhoC vaccine synthetic long peptide vaccine targeting Ras homolog gene family member C (RhoC)…”

Section: Discussionmentioning

confidence: 99%

Application of Nanotechnology in Therapeutic Cancer Vaccines

Guo

Tang

et al. 2023

Advanced NanoBiomed Research

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Cancer can significantly lower the quality of life of human beings. Numerous treatments have thus far been developed to treat cancer, namely, surgery, radiotherapy, and chemotherapy. [1] Cancer treated with surgery has a high chance of recurrence because the boundary between the malignant tumor and the surrounding tissues and organs is indistinct. This problem also increases the probability of lymphatic and hematogenous metastasis. [2] Radiotherapy and chemotherapy eliminate not only tumor cells but also normal cells, causing harm to patients. Cancer can trigger tumor-specific immune responses, which has spurred the development of cancer vaccines. [3] Cancer vaccines can induce tumor regression or prevent tumor formation while establishing an enduring antitumor memory effect. [4] 1.1. Basic Concepts Cancer vaccines typically include tumor antigens, adjuvants, and delivery vehicles. The effectiveness of cancer vaccines primarily relies on three critical steps (Figure 1): 1) antigen uptake by antigenpresenting cells (APCs); 2) presentation of antigens to T cells by APC, followed by T cell activation; and 3) elimination of tumors by effector T cells. [5] Poor stability of antigens, immune escape, and low immunogenicity hinder the development of cancer vaccines. [6] Adjuvants that can improve the adaptive immune response of the body to antigens have been developed in response to the weak immunogenicity of cancer vaccines. [7] They enhance immune responses to tumor antigens, [8] as well as effectively avoid the immune suppression produced by the body, [9] thereby improving the immunotherapy efficiency of cancer vaccines. Aluminum salt adjuvants, pattern recognition receptor agonists, and polypeptides, among others, exhibit good immune activation. [10] Polymeric nanoparticles provide a promising platform for delivering adjuvants that can enhance antigen uptake by adjusting physical and chemical properties, including shape, size, electrical properties, polarity, processing, and presentation. [11] In addition, nanoadjuvants can enhance the stability of antigens and influence the release kinetics of cancer vaccines. [12] Tumor antigens can be classified as tumor-associated antigens (TAAs) and tumor-specific antigens (TSAs). [13] TAAs are more highly expressed in tumor cells than in normal tissues but lack complete specificity for tumors. In contrast, TSAs are abnormal proteins produced by cancer cells via nonsynonymous mutations. [14] TSAs are expressed on tumor cells and are relatively highly immunogenic. [15] The high safety and the reduced off-target side effects render TSAs ideal as targets for tumor immunotherapy. [16] With the rapid development of genomics and bioinformatics, the screening and identification of TSAs are more accurate and faster. Cancer therapeutic vaccines based on TSAs have demonstrated clinical efficacy and exhibited good application prospects. [17] History and Current SituationThe history of tumor antigens and cancer vaccines is summarized in Figure 2. William Coley discovered a mixed bacterial

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Section: Discussionmentioning

confidence: 99%

Application of Nanotechnology in Therapeutic Cancer Vaccines

Guo

Tang

et al. 2023

Advanced NanoBiomed Research

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“…Clinical trials have demonstrated the safety and tolerability of the WT1 peptide-based vaccine in humans, as well as the induction of WT1-specific IgG antibodies [ 26 , 27 , 28 ]. In this context, research is still ongoing [ 29 , 30 ].…”

Section: Vaccine Therapymentioning

confidence: 99%

Glioblastoma Vaccines as Promising Immune-Therapeutics: Challenges and Current Status

Squalli Houssaini,

Lamrabet,

Nshizirungu

et al. 2024

Vaccines

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Glioblastoma (GBM) is the most common and aggressive malignant brain tumor. Standard treatments including surgical resection, radiotherapy, and chemotherapy, have failed to significantly improve the prognosis of glioblastoma patients. Currently, immunotherapeutic approaches based on vaccines, chimeric antigen-receptor T-cells, checkpoint inhibitors, and oncolytic virotherapy are showing promising results in clinical trials. The combination of different immunotherapeutic approaches is proving satisfactory and promising. In view of the challenges of immunotherapy and the resistance of glioblastomas, the treatment of these tumors requires further efforts. In this review, we explore the obstacles that potentially influence the efficacy of the response to immunotherapy and that should be taken into account in clinical trials. This article provides a comprehensive review of vaccine therapy for glioblastoma. In addition, we identify the main biomarkers, including isocitrate dehydrogenase, epidermal growth factor receptor, and telomerase reverse transcriptase, known as potential immunotherapeutic targets in glioblastoma, as well as the current status of clinical trials. This paper also lists proposed solutions to overcome the obstacles facing immunotherapy in glioblastomas.

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“…The resulting data demonstrated the induction of WT1-specific IgG antibodies as well as the identification of a potential biomarker [ 35 , 36 ]. This is still an actively researched approach [ 37 , 38 ].…”

Section: Established Immunotherapeutic Approaches: Enhancing T-cell A...mentioning

confidence: 99%

Next Steps for Immunotherapy in Glioblastoma

Cao

Wainwright

Lee-Chang

et al. 2022

Cancers

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Outcomes for glioblastoma (GBM) patients undergoing standard of care treatment remain poor. Here we discuss the portfolio of previously investigated immunotherapies for glioblastoma, including vaccine therapy and checkpoint inhibitors, as well as novel emerging therapeutic approaches. In addition, we explore the factors that potentially influence response to immunotherapy, which should be considered in future research aimed at improving immunotherapy efficacy.

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A phase I study of the WT2725 dosing emulsion in patients with advanced malignancies

Cited by 8 publications

References 48 publications

Application of Nanotechnology in Therapeutic Cancer Vaccines

Application of Nanotechnology in Therapeutic Cancer Vaccines

Glioblastoma Vaccines as Promising Immune-Therapeutics: Challenges and Current Status

Next Steps for Immunotherapy in Glioblastoma

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