Clinical Evaluation of a Personalized Vaccine Immunotherapy in Combination with Checkpoint Inhibitors for Triple Negative Breast Cancer

个性化疫苗免疫疗法联合检查点抑制剂治疗三阴性乳腺癌的临床评价

基本信息

  • 批准号:
    10551635
  • 负责人:
  • 金额:
    $ 3.46万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-02-01 至 2023-08-31
  • 项目状态:
    已结题

项目摘要

Abstract of the supplemental grant: Breast cancer accounts for the highest cancer-related mortality in women. Among its subtypes, metastatic triple negative breast cancer (TNBC) has the worst prognosis largely due to resistance to currently available therapies and lack of estrogen receptor, progesterone receptor and HER-2 protein expression. Recent studies employing immune checkpoint inhibitor (ICI) therapies suggest that TNBC may be a good target for ICI therapy due to the presence of high level of infiltrating lymphocytes. However, the majority of the TNBC cancer patients do not respond to ICI therapy due to the lack of pre-existing immunity. In order to develop more effective treatments, it is important to design a therapeutic approach for TNBC patients which overcomes intra-tumoral and inter-patient heterogeneity. Metaclipse Therapeutics has been engaged in developing a personalized vaccine to address heterogeneity. Utilizing a novel protein transfer method, we generate tumor membrane vesicles (TMVs) derived from whole tumor tissues and modify them with glycolipid-anchored forms of immunostimulatory molecules (GPI- ISMs) expressing B7-1 and interleukin-12 (IL-12). Our data demonstrates that TMV vaccines prepared from syngeneic tumors are effective in multiple murine models of cancer. However, it is currently unknown if neoadjuvant chemotherapy which is a standard of care for breast cancer affects the yield and quality of TMV- based vaccines. We hypothesize that the addition of standard-of-care (SOC) chemotherapy which is usually administered in TNBC patients before surgery impacts the yield and quality of TMV-based vaccines. To address this, the following specific aims are proposed. Aim 1, To define the impact of neoadjuvant chemotherapy on the yield and quality of the TMV vaccine. Aim 2, To define the impact of neoadjuvant chemotherapy on the ability of TMV vaccine to stimulate APCs and autologous T cells ex vivo. The parent grant of this supplement proposal will be conducting Phase 1 clinical trial to evaluate the tolerability of TMV vaccine in TNBC patients. This study will provide an understanding about how the neoadjuvant chemotherapy impacts the TMV-based vaccines prepared from TNBC tumors.
补充补助金摘要: 乳腺癌是妇女癌症相关死亡率最高的疾病。在其亚型中,转移性三重 阴性乳腺癌(TNBC)具有最差的预后,这主要是由于对目前可用的疗法的抗性 雌激素受体、孕激素受体和HER-2蛋白表达缺失。最近的研究采用 免疫检查点抑制剂(ICI)疗法表明,TNBC可能是ICI疗法的良好靶点, 存在高水平的浸润性淋巴细胞。然而,大多数TNBC癌症患者并不 由于缺乏预先存在的免疫力,对ICI治疗有反应。为了开发更有效的治疗方法,它 重要的是为TNBC患者设计一种治疗方法, 异质性Metaclipse Therapeutics一直致力于开发个性化疫苗,以解决 异质性利用一种新的蛋白质转移方法,我们产生了肿瘤膜囊泡(TMV), 从整个肿瘤组织,并修改他们与糖脂锚定形式的免疫刺激分子(GPI- ISMs)表达B7-1和白细胞介素-12(IL-12)。我们的数据表明,TMV疫苗制备从 同基因肿瘤在多种小鼠癌症模型中有效。然而,目前尚不清楚, 作为乳腺癌标准治疗的新辅助化疗影响TMV的产量和质量, 基于疫苗。我们假设,增加标准治疗(SOC)化疗,这通常是 在手术前在TNBC患者中施用TMV影响基于TMV的疫苗的产量和质量。解决 为此,提出以下具体目标。目的1,明确新辅助化疗对原发性肝癌的影响, TMV疫苗的产量和质量。目的2,明确新辅助化疗对原发性肝癌患者化疗能力的影响, TMV疫苗以离体刺激APC和自体T细胞。本补充提案的母基金 将进行第一阶段临床试验,以评估TMV疫苗在TNBC患者中的耐受性。本研究 将提供关于新辅助化疗如何影响基于TMV的疫苗的理解 由TNBC肿瘤制备。

项目成果

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CHRISTOPHER D PACK其他文献

CHRISTOPHER D PACK的其他文献

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{{ truncateString('CHRISTOPHER D PACK', 18)}}的其他基金

Clinical Evaluation of a Personalized Vaccine Immunotherapy in Combination with Checkpoint Inhibitors for Triple Negative Breast Cancer
个性化疫苗免疫疗法联合检查点抑制剂治疗三阴性乳腺癌的临床评价
  • 批准号:
    10489848
  • 财政年份:
    2021
  • 资助金额:
    $ 3.46万
  • 项目类别:
Clinical Evaluation of a Personalized Vaccine Immunotherapy in Combination with Checkpoint Inhibitors for Triple Negative Breast Cancer
个性化疫苗免疫疗法联合检查点抑制剂治疗三阴性乳腺癌的临床评价
  • 批准号:
    10687287
  • 财政年份:
    2021
  • 资助金额:
    $ 3.46万
  • 项目类别:
Clinical Evaluation of a Personalized Vaccine Immunotherapy in Combination with Checkpoint Inhibitors for Triple Negative Breast Cancer
个性化疫苗免疫疗法联合检查点抑制剂治疗三阴性乳腺癌的临床评价
  • 批准号:
    10254572
  • 财政年份:
    2021
  • 资助金额:
    $ 3.46万
  • 项目类别:
Membrane-based immunotherapy for triple negative breast cancer- a partnered approach
基于膜的三阴性乳腺癌免疫疗法——一种合作方法
  • 批准号:
    9895637
  • 财政年份:
    2016
  • 资助金额:
    $ 3.46万
  • 项目类别:
Membrane-based immunotherapy for triple negative breast cancer- a partnered approach
基于膜的三阴性乳腺癌免疫疗法——一种合作方法
  • 批准号:
    10247102
  • 财政年份:
    2016
  • 资助金额:
    $ 3.46万
  • 项目类别:
A membrane-based immunotherapy for triple negative breast cancer
针对三阴性乳腺癌的基于膜的免疫疗法
  • 批准号:
    8524714
  • 财政年份:
    2013
  • 资助金额:
    $ 3.46万
  • 项目类别:
Regulation of CD8 T cell responses to polyoma virus infection
CD8 T 细胞对多瘤病毒感染反应的调节
  • 批准号:
    7546027
  • 财政年份:
    2008
  • 资助金额:
    $ 3.46万
  • 项目类别:

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