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Detection method of triple negative breast cancer immunotherapy curative effect prediction marker CCL19

A technology for triple-negative breast cancer and immunotherapy, applied in the biological field, can solve the problems of poor prediction effect, low accuracy, and impossibility of popularization of immunotherapy curative effect biomarkers, and achieve accurate prediction of immunotherapy curative effect and low cost Effect

Pending Publication Date: 2022-08-05
FUDAN UNIV SHANGHAI CANCER CENT
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the currently proposed biomarkers for immunotherapy efficacy are poorly predictive, and most of them are based on high-throughput sequencing, which cannot be popularized in the clinic
The existing PD-1 kits and PD-L1 kits are convenient and fast, but the accuracy rate is low, and they cannot identify patients who benefit from immunotherapy

Method used

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  • Detection method of triple negative breast cancer immunotherapy curative effect prediction marker CCL19
  • Detection method of triple negative breast cancer immunotherapy curative effect prediction marker CCL19
  • Detection method of triple negative breast cancer immunotherapy curative effect prediction marker CCL19

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0048] Example 1 Discovery and functional verification of CCL19 molecules

[0049] Dendritic cells (DCs) are the most important antigen-presenting cells, which can initiate T cell-mediated immune responses, but their role in tumor immunotherapy is not yet clear. Based on single-cell sequencing, multi-omics analysis, in vivo experiments and clinical trial validation, the present invention identifies a key DC subset that can predict TNBC immunotherapy response, namely CCL19 + DC (Examples 1.1 and 1.2). After validation by multiple external cohorts, CCL19 + DCs were shown to be widespread in breast cancer tissue, enriched in TNBC and suggest anti-tumor immune activation (Examples 1.3 and 1.4). More critically, we used CCL19 to characterize CCL19 + DC to simplify clinical application, found that CCL19 is mainly composed of CCL19 + DC secretion, and by promoting CD8 + T cells function to exert anti-tumor immunity (Examples 1.5 and 1.6). Therefore, CCL19 molecule can be used a...

Embodiment 2

[0077] Example 2 Serum CCL19 level in peripheral blood of TNBC patients before treatment as a predictive marker of ICI efficacy

[0078] ELISA kit was used to detect the level of CCL19 in the serum of patients with metastatic TNBC before receiving immunotherapy, and it was found that the expression level of serum CCL19 before treatment could predict the benefit of immunotherapy. The specific verification process includes the following steps:

[0079] 1) Study cohort

[0080] We collected sera from 18 patients with metastatic TNBC treated with camrelizumab (PD-1 monoclonal antibody) in the FUTURE clinical trial (international registration number NCT03805399) before and after treatment, using an ELISA kit (Abecam). , Cat. No. ab100601) detected serum CCL19 levels in patients ( Figure 19 ). The immune response assessment can be divided into clinical remission (the sum of CR and PR) and clinical non-remission (the sum of PD and SD). The serum CCL19 concentration before treatm...

Embodiment 3

[0084] Example 3 Immunohistochemical staining of paraffin sections of tumor tissue from TNBC patients before treatment to detect CCL19 as a predictive marker for ICI efficacy

[0085] Immunohistochemistry was used to detect the level of CCL19 in the tissue of patients with metastatic TNBC before receiving immunotherapy, and it was found that the expression level of CCL19 in the tumor tissue before treatment could predict the benefit of immunotherapy.

[0086] We collected pre-treatment paraffin sections from 30 camrelizumab-based patients with advanced TNBC in the FUTURE-C-Plus clinical trial (international registration number NCT04129996), using CCL19 antibody (Sigma, Cat. No. HPA067758, diluted Multiples of 1:200), immunohistochemical staining (the experimental platform was Ventana Benchmark ULTRA detection system), CCL19 positive cells / total cells ≥ 1% were defined as CCL19 positive, and the relationship between it and the efficacy of patients was evaluated. Among the 29 pa...

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Abstract

The invention relates to a detection method of a triple negative breast cancer immunotherapy curative effect prediction marker CCL19. The invention provides application of CCL19 as a marker in preparation of a breast cancer immunotherapy curative effect and / or prognosis prediction product. The invention also provides a triple negative breast cancer immunotherapy curative effect and prognosis prediction kit comprising a CCL19 protein detection reagent and an optional specification. The invention also provides application of the CCL19 molecule combined with a second therapeutic agent in preparation of antitumor drugs. The blank of liquid biopsy for predicting the curative effect of triple negative breast cancer immunotherapy is greatly filled, and accurate prediction of the curative effect of the immunotherapy is realized in a non-invasive, rapid and low-cost manner.

Description

technical field [0001] The invention belongs to the field of biotechnology, and in particular relates to the application of CCL19 as a marker in preparing a product for predicting the efficacy and / or prognosis of breast cancer immunotherapy. Background technique [0002] Triple negative breast cancer (TNBC) refers to a type of breast cancer with negative expression of estrogen (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). 15%-20%. Compared with hormone receptor-positive breast cancer patients, TNBC patients tend to have younger age of onset, are more prone to visceral metastasis, have a higher risk of postoperative recurrence and have a poorer prognosis, which is a difficulty in clinical treatment. [0003] Because TNBC lacks expression of key receptors, patients do not benefit from targeted therapy. The advent of immunotherapy has brought a breakthrough in the treatment of TNBC. Immunotherapy mainly includes vaccines, immune checkp...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N33/574A61K38/19A61K39/395A61P35/00
CPCG01N33/57415G01N33/57484A61K38/195A61K39/3955A61P35/00G01N2333/523A61K2300/00
Inventor 邵志敏江一舟金希吴松阳张思维马丁
Owner FUDAN UNIV SHANGHAI CANCER CENT
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