100 项与 HER2-antigen specific cancer vaccine 相关的专利（医药）
项与 HER2-antigen specific cancer vaccine 相关的文献（医药）
2023-04-24·Clinical cancer research : an official journal of the American Association for Cancer Research
A Phase I/II trial of HER-2/neu vaccine primed autologous T-cell infusions in patients with treatment refractory HER-2/neu overexpressing breast cancer.
作者: Mary L Disis ; Yushe Dang ; Andrew L Coveler ; Jennifer S Childs ; Doreen M Higgins ; Ying Liu ; Jing Zhou ; Sean Mackay ; Lupe G Salazar
High levels of Type I T-cells are needed for tumor eradication. We evaluated whether the HER2 specific vaccine primed T-cells are readily expanded ex vivo to achieve levels needed for therapeutic infusion.
PATIENTS AND METHODS:
Phase I/II non-randomized trial of escalating doses of ex-vivo expanded HER2 specific T-cells after in vivo priming with a multiple peptide-based HER2 intracellular domain vaccine. Vaccines were given weekly for a total of 3 immunizations. Two weeks after the third vaccine, patients underwent leukapheresis for T-cell expansion, then received 3 escalating cell doses over 7-10-day intervals. Booster vaccines were administered after the T-cell infusions. The primary objective was safety. The secondary objectives included extent and persistence of HER2 specific T-cells, development of epitope spreading, and clinical response. Patients received a CT scan prior to enrollment and 1 month after the last T-cell infusion.
Nineteen patients received T-cell infusions. Treatment was well tolerated. One month after the last T-cell infusion, 82% of patients had significantly augmented T-cells to at least one of the immunizing epitopes and 81% of patients demonstrated enhanced intramolecular epitope spreading compared to baseline (p<0.05). There were no complete responses, one partial response (6%) and eight patients with stable disease (47%) for a disease control rate of 53%. The median survival for those with progressive disease was 20.5 months and for responders (PR+SD) was 45.0 months.
Adoptive transfer of HER2 vaccine primed T-cells was feasible, associated with minimal toxicity, and resulted in an increased overall survival in responding patients.
2021-12-06·The Cochrane database of systematic reviews2区 · 医学
Immunotherapy (excluding checkpoint inhibitors) for stage I to III non-small cell lung cancer treated with surgery or radiotherapy with curative intent.
2区 · 医学
作者: Jianwei Zhu ; Yun Yuan ; Xiaoyu Wan ; Dan Yin ; Rui Li ; Wenwen Chen ; Chen Suo ; Huan Song
Non-small cell lung cancer (NSCLC) is the most common lung cancer, accounting for approximately 80% to 85% of all cases. For people with localised NSCLC (stages I to III), it has been speculated that immunotherapy may be helpful for reducing postoperative recurrence rates, or improving the clinical outcomes of current treatment for unresectable tumours. This is an update of a Cochrane Review first published in 2017 and it includes two new randomised controlled trials (RCTs).
To assess the effectiveness and safety of immunotherapy (excluding checkpoint inhibitors) among people with localised NSCLC of stages I to III who received curative intent of radiotherapy or surgery.
We searched the following databases (from inception to 19 May 2021): CENTRAL, MEDLINE, Embase, CINAHL, and five trial registers. We also searched conference proceedings and reference lists of included trials.
We included RCTs conducted in adults (≥ 18 years) diagnosed with NSCLC stage I to III after surgical resection, and those with unresectable locally advanced stage III NSCLC receiving radiotherapy with curative intent. We included participants who underwent primary surgical treatment, postoperative radiotherapy or chemoradiotherapy if the same strategy was provided for both intervention and control groups.
DATA COLLECTION AND ANALYSIS:
Two review authors independently selected eligible trials, assessed risk of bias, and extracted data. We used survival analysis to pool time-to-event data, using hazard ratios (HRs). We used risk ratios (RRs) for dichotomous data, and mean differences (MDs) for continuous data, with 95% confidence intervals (CIs). Due to clinical heterogeneity (immunotherapeutic agents with different underlying mechanisms), we combined data by applying random-effects models.
We included 11 RCTs involving 5128 participants (this included 2 new trials with 188 participants since the last search dated 20 January 2017). Participants who underwent surgical resection or received curative radiotherapy were randomised to either an immunotherapy group or a control group. The immunological interventions were active immunotherapy Bacillus Calmette-Guérin (BCG) adoptive cell transfer (i.e. transfer factor (TF), tumour-infiltrating lymphocytes (TIL), dendritic cell/cytokine-induced killer (DC/CIK), antigen-specific cancer vaccines (melanoma-associated antigen 3 (MAGE-A3) and L-BLP25), and targeted natural killer (NK) cells. Seven trials were at high risk of bias for at least one of the risk of bias domains. Three trials were at low risk of bias across all domains and one small trial was at unclear risk of bias as it provided insufficient information. We included data from nine of the 11 trials in the meta-analyses involving 4863 participants. There was no evidence of a difference between the immunotherapy agents and the controls on any of the following outcomes: overall survival (HR 0.94, 95% CI 0.84 to 1.05; P = 0.27; 4 trials, 3848 participants; high-quality evidence), progression-free survival (HR 0.94, 95% CI 0.86 to 1.03; P = 0.19; moderate-quality evidence), adverse events (RR 1.12, 95% CI 0.97 to 1.28; P = 0.11; 4 trials, 4126 evaluated participants; low-quality evidence), and severe adverse events (RR 1.14, 95% CI 0.92 to 1.40; 6 trials, 4546 evaluated participants; low-quality evidence). Survival rates at different time points showed no evidence of a difference between immunotherapy agents and the controls. Survival rate at 1-year follow-up (RR 1.02, 95% CI 0.96 to 1.08; I2 = 57%; 7 trials, 4420 participants; low-quality evidence), 2-year follow-up (RR 1.02, 95% CI 0.93 to 1.12; 7 trials, 4420 participants; moderate-quality evidence), 3-year follow-up (RR 0.99, 95% CI 0.90 to 1.09; 7 trials, 4420 participants; I2 = 22%; moderate-quality evidence) and at 5-year follow-up (RR 0.98, 95% CI 0.86 to 1.12; I2 = 0%; 7 trials, 4389 participants; moderate-quality evidence). Only one trial reported overall response rates. Two trials provided health-related quality of life results with contradicting results. AUTHORS' CONCLUSIONS: Based on this updated review, the current literature does not provide evidence that suggests a survival benefit from adding immunotherapy (excluding checkpoint inhibitors) to conventional curative surgery or radiotherapy, for people with localised NSCLC (stages I to III). Several ongoing trials with immune checkpoints inhibitors (PD-1/PD-L1) might bring new insights into the role of immunotherapy for people with stages I to III NSCLC.
2021-06-10·Cancers2区 · 医学
Development of a Virus-Like Particle-Based Anti-HER2 Breast Cancer Vaccine.
2区 · 医学
作者: He Hu ; Nicole F Steinmetz
To develop a human epidermal growth factor receptor-2 (HER2)-specific cancer vaccine, using a plant virus-like particle (VLP) platform. Copper-free click chemistry and infusion encapsulation protocols were developed to prepare VLPs displaying the HER2-derived CH401 peptide epitope, with and without Toll-like receptor 9 (TLR9) agonists loaded into the interior cavity of the VLPs; Physalis mottle virus (PhMV)-based VLPs were used. After prime-boost immunization of BALB/c mice through subcutaneous administration of the vaccine candidates, sera were collected and analyzed by enzyme-linked immunosorbent assay (ELISA) for the CH401-specific antibodies; Th1 vs. Th2 bias was determined by antibody subtyping and splenocyte assay. Efficacy was assessed by tumor challenge using DDHER2 tumor cells. We successful developed two VLP-based anti-HER2 vaccine candidates-PhMV-CH401 vs. CpG-PhMV-CH401; however, the addition of the CpG adjuvant did not confer additional immune priming. Both VLP-based vaccine candidates elicited a strong immune response, including high titers of HER2-specific immunoglobulins and increased toxicity of antisera to DDHER2 tumor cells. DDHER2 tumor growth was delayed, leading to prolonged survival of the vaccinated vs. naïve BALB/C mice. The PhMV-based anti-HER2 vaccine PhMV-CH401, demonstrated efficacy as an anti-HER2 cancer vaccine. Our studies highlight that VLPs derived from PhMV are a promising platform to develop cancer vaccines.