个性化肽免疫治疗后HER2阳性转移性乳腺癌患者生存率提高
Improved Survival of a HER2-Positive Metastatic Breast Cancer Patient Following a Personalized Peptide Immunization.
作者信息
Schönharting Wolfgang, Roehnisch Tim, Manoochehri Mehdi, Christoph Jan, Sieger Marie, Nogueira Mauro, Martos-Contreras Mari Carmen, Kunz Meik
机构信息
PMCR GmbH, 76135 Karlsruhe, Germany.
Interdisziplinäres Onkologisches Zentrum (IOZ), 80336 Munich, Germany.
出版信息
Vaccines (Basel). 2023 May 25;11(6):1023. doi: 10.3390/vaccines11061023.
Cancer neoantigens that arise from somatic mutations have emerged as important targets for personalized immunization. Here, we report an improved overall survival of a HER2-positive metastatic breast cancer patient using a bioinformatic-based personalized peptide immunization called BITAP (BioInformatic Tumor Address Peptides). The epitopes were predicted using our in-house bioinformatic pipeline, and the immunogenicity was tested by IFN-γ ELISPOT and intracellular cytokine staining assays. In total, a significant peptide-specific T-cell response was detected against 18 out of the 76 (≈24%) tested peptides. The patient's follow-up by measuring serologic markers showed a significant reduction in the tumor marker levels following BITAP immunization. Along with standard treatment, the patient treated with the BITAP showed stable disease with a remarkably improved overall survival, and no serious treatment-related adverse effects. In conclusion, our findings suggest that BITAP immunization is feasible, and safe, and may induce tumor regressions in patients with HER2-positive subsets of breast cancer.
由体细胞突变产生的癌症新抗原已成为个性化免疫的重要靶点。在此,我们报告了一名HER2阳性转移性乳腺癌患者通过使用基于生物信息学的个性化肽免疫疗法BITAP(生物信息学肿瘤靶向肽)实现了总生存期的改善。使用我们内部的生物信息学流程预测表位,并通过IFN-γ ELISPOT和细胞内细胞因子染色试验测试免疫原性。总共,在76个测试肽中的18个(约24%)中检测到了显著的肽特异性T细胞反应。通过测量血清学标志物对患者进行随访,结果显示BITAP免疫后肿瘤标志物水平显著降低。除标准治疗外,接受BITAP治疗的患者疾病稳定,总生存期显著改善,且未出现严重的治疗相关不良反应。总之,我们的研究结果表明,BITAP免疫是可行且安全的,可能会使HER2阳性乳腺癌亚组患者出现肿瘤消退。