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Sendai virus-based immunoadjuvant in hydrogel vaccine intensity-modulated dendritic cells activation for suppressing tumorigenesis.

ABSTRACT: The conventional immunoadjuvants in vaccine have weak effect on stimulating antigen presentation and activating anti-tumor immunity. Unexpectedly, we discovered that non-pathogenic Sendai virus (SeV) could activate antigen-presenting cells (APCs) represented by dendritic cells (DCs). Here, we designed an injectable SeV-based hydrogel vaccine (SHV) to execute multi-channel recruitment and stimulation of DCs for boosting the specific immune response against tumors. After the release of the NIR-triggered antigens from tumor cells, dendritic cells around the vaccine efficiently transport the antigens to lymph nodes and present them to T lymphocytes, thereby inducing systemic anti-tumor immune memory. Our findings demonstrated that the SHV with excellent universality, convenience and flexibility has achieved better immune protection effects in inhibiting the occurrence of melanoma and breast cancer. In conclusion, the SHV system might serve as the next generation of personalized anti-tumor vaccines with enhanced features over standard vaccination regimens, and represented an alternative way to suppress tumorigenesis.

SUBMITTER: Zheng B

PROVIDER: S-EPMC8076650 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Sendai virus-based immunoadjuvant in hydrogel vaccine intensity-modulated dendritic cells activation for suppressing tumorigenesis.

Zheng Bin B Peng Wenchang W Gan Lin L Guo Mingming M Wang Shuchao S Zhang Xiao-Dong XD Ming Dong D

Bioactive materials 20210413 11

The conventional immunoadjuvants in vaccine have weak effect on stimulating antigen presentation and activating anti-tumor immunity. Unexpectedly, we discovered that non-pathogenic Sendai virus (SeV) could activate antigen-presenting cells (APCs) represented by dendritic cells (DCs). Here, we designed an injectable SeV-based hydrogel vaccine (SHV) to execute multi-channel recruitment and stimulation of DCs for boosting the specific immune response against tumors. After the release of the NIR-tri ...[more]

PMID: 33937591

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Project description:PurposeWe compared work outcomes in patients with oropharyngeal cancer (OPC), randomized to intensity-modulated proton (IMPT) versus intensity-modulated photon therapy (IMRT) for chemoradiation therapy (CRT).Patients and methodsIn 147 patients with stage II-IVB squamous cell OPC participating in patient-reported outcomes assessments, a prespecified secondary aim of a randomized phase II/III trial of IMPT (n = 69) versus IMRT (n = 78), we compared absenteeism, presenteeism (i.e., the extent to which an employee is not fully functional at work), and work productivity losses. We used the work productivity and activity impairment questionnaire at baseline (pre-CRT), at the end of CRT, and at 6 months, 1 year, and 2 years. A one-sided Cochran-Armitage test was used to analyze within-arm temporal trends, and a χ2 test was used to compare between-arm differences. Among working patients, at each follow-up point, a 1-sided Wilcoxon rank-sum test was used to compare work-productivity scores.ResultsPatient characteristics in IMPT versus IMRT arms were similar. In the IMPT arm, within-arm analysis demonstrated that an increasing proportion of patients resumed working after IMPT, from 60% (40 of 67) pre-CRT and 71% (30 of 42) at 1 year to 78% (18 of 23) at 2 years (P = 0.025). In the IMRT arm, the proportion remained stable, with 57% (43 of 76) pre-CRT, 54% (21 of 39) at 1 year, and 52% (13 of 25) working at 2 years (P = 0.47). By 2 years after CRT, the between-arm difference between patients who had IMPT and those who had IMRT trended toward significance (P = 0.06). Regardless of treatment arm, among working patients, the most severe work impairments occurred from treatment initiation to the end of CRT, with significant recovery from absenteeism, presenteeism, and productivity impairments by the 2-year follow-up (P < 0.001 for all). Higher magnitudes of recovery from absenteeism (at 1 year, P = 0.05; and at 2 years, P = 0.04) and composite work impairment scores (at 1 year, P = 0.04; and at 2 years, P = 0.04) were seen in patients treated with IMPT versus those treated with IMRT.ConclusionIn patients with OPC receiving curative CRT, patients randomized to IMPT demonstrated increasing work and productivity recovery trends. Studies are needed to identify mechanisms underlying head and neck CRT treatment causing work disability and impairment.

Project description:This paper presents a concept for a proton therapy system capable of delivering intensity modulated proton therapy using a fan beam of protons. This system would allow present and future gantry-based facilities to deliver state-of-the-art proton therapy with the greater normal tissue sparing made possible by intensity modulation techniques.A method for producing a divergent fan beam of protons using a pair of electromagnetic quadrupoles is described and particle transport through the quadrupole doublet is simulated using a commercially available software package. To manipulate the fan beam of protons, a modulation device is developed. This modulator inserts or retracts acrylic leaves of varying thickness from subsections of the fan beam. Each subsection, or beam channel, creates what effectively becomes a beam spot within the fan area. Each channel is able to provide 0-255 mm of range shift for its associated beam spot, or stop the beam and act as an intensity modulator. Results of particle transport simulations through the quadrupole system are incorporated into the MCNPX Monte Carlo transport code along with a model of the range and intensity modulation device. Several design parameters were investigated and optimized, culminating in the ability to create topotherapy treatment plans using distal-edge tracking on both phantom and patient datasets.Beam transport calculations show that a pair of electromagnetic quadrupoles can be used to create a divergent fan beam of 200 MeV protons over a distance of 2.1 m. The quadrupole lengths were 30 and 48 cm, respectively, with transverse field gradients less than 20 T/m, which is within the range of water-cooled magnets for the quadrupole radii used. MCNPX simulations of topotherapy treatment plans suggest that, when using the distal edge tracking delivery method, many delivery angles are more important than insisting on narrow beam channel widths in order to obtain conformal target coverage. Overall, the sharp distal falloff of a proton depth-dose distribution was found to provide sufficient control over the dose distribution to meet objectives, even with coarse lateral resolution and channel widths as large as 2 cm. Treatment plans on both phantom and patient data show that dose conformity suffers when treatments are delivered from less than approximately ten angles. Treatment time for a sample prostate delivery is estimated to be on the order of 10 min, and neutron production is estimated to be comparable to that found for existing collimated systems.Fan beam proton therapy is a method of delivering intensity modulated proton therapy which may be employed as an alternative to magnetic scanning systems. A fan beam of protons can be created by a set of quadrupole magnets and modified by a dual-purpose range and intensity modulator. This can be used to deliver inversely planned treatments, with spot intensities optimized to meet user defined dose objectives. Additionally, the ability of a fan beam delivery system to effectively treat multiple beam spots simultaneously may provide advantages as compared to spot scanning deliveries.

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Sendai virus-based immunoadjuvant in hydrogel vaccine intensity-modulated dendritic cells activation for suppressing tumorigenesis.

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Sendai virus-based immunoadjuvant in hydrogel vaccine intensity-modulated dendritic cells activation for suppressing tumorigenesis.

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