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Method and composition for predicting long-term survival in cancer immunotherapy

A cancer immunity, medium and long-term technology, applied in the field of cancer treatment, can solve the problem of high toxicity of combination therapy

Pending Publication Date: 2021-11-26
SAITAMA MEDICAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although the development of combination therapy of PD-1 inhibitors with cytotoxic anticancer agents or other immune checkpoint inhibitors is underway, the combination therapy has the problem of high toxicity

Method used

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  • Method and composition for predicting long-term survival in cancer immunotherapy
  • Method and composition for predicting long-term survival in cancer immunotherapy
  • Method and composition for predicting long-term survival in cancer immunotherapy

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0710] (Example 1: Nivolumab treatment process)

[0711] For patients with advanced lung cancer who have been treated with anti-PD-1 antibody, nivolumab, from the beginning of treatment to 5 years later, based on Brahmer et al. (Five-year follow-up from theCA209-003 study of nivolumab in previously treated advanced non-small celllung cancer: clinical characteristics of long-term survivors. Presented at: 2017AACR Annual Meeting; April 1-5, 2017; Washington, DC. Abstract CTO77), the inventor conducted seminar.

[0712] In the left panel, the curve representing overall survival does not decline from around year 3, with 5-year survival accounting for 16% of the total. The blue bar of the swim lane diagram (Swimplot) in the right figure indicates the treatment period. In this clinical trial, 12 of 16 (#1, 2, 3, 4, 6, 7, 8, 9, 10, 11, 12, and 13) who ended treatment within 2 years but survived 5 years After the end of nivolumab treatment, he survived without any treatment for mor...

Embodiment 2

[0715] (Example 2: FACS Calibur Analysis)

[0716] FACS Calibur analysis was performed using the following sequence.

[0717] (1) From blood collection to cryopreservation

[0718] -About 14 to 16 mL of blood was collected in two 7 to 8 mL vacuum blood collection tubes (containing heparin) manufactured by Becton-Dickinson (BD).

[0719] - Within 2 hours to half a day after blood collection, centrifuge at 3200 rpm for 20 minutes at room temperature (18-25°C).

[0720] - After plasma collection, the plasma components and cellular components remaining on the upper layer of the gel barrier were stirred and collected by a pipette, and collected in 50 mL centrifuge tubes (collected in 1 from two blood collection tubes). The collected volume (about 13 mL) and an equal amount of PBS (+10% FBS) were added.

[0721] - Centrifuge at 1600 rpm for 5 minutes at 4°C.

[0722] - Discard the supernatant after centrifugation, and suspend in 4.5 ml of cellbanker 2 solution manufactured by Ni...

Embodiment 3

[0744] (Example 3: ROC analysis and PFS drawing)

[0745] exist Figure 4 The left side of the graph shows the results of ROC analysis on the data obtained in Example 2. That is, in the stratified analysis of the progression-free survival group over 18 months, it was shown that CD62L low CD4 + When the ratio of T cells >35.85 was used as the threshold, it could be predicted with a sensitivity of 85.7% and a specificity of 83.3%. AUC was also very good at 0.896.

[0746] CD62L low CD4 + The results of plotting the ratio of T cells on the horizontal axis and the days of progression-free survival (PFS (days)) on the vertical axis are shown in Figure 4 to the right of the . CD62L low CD4 + When the ratio of T cells is less than 20%, most of them belong to the early disease exacerbation group, and when it is more than 35.85%, more than half of them belong to the long-term survival group.

[0747] These results suggest that CD62L low CD4 + T cell proportion is an excell...

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Abstract

Provided is a peripheral blood biomarker for predicting the long-term survival / need for therapeutic intervention in cancer immunotherapy. The present invention provides a method that uses a composition of a cell subpopulation in a sample obtained from a subject as an indicator to predict the long-term survival of the subject in cancer immunotherapy. The long-term survival / need for therapeutic intervention in a subject in cancer immunotherapy can be predicted by comparing the level of a CD4+ T cell subpopulation that correlates with dendritic cell stimulation in an antitumor immune response or a dendritic cell subpopulation that correlates with dendritic cell stimulation in an antitumor immune response with a reference standard.

Description

technical field [0001] The present invention relates to the field of cancer therapy. Specifically, it concerns the prediction of long-term survival in cancer immunotherapy. Background technique [0002] The effectiveness of immune checkpoint inhibitors with PD-1 / PD-L1 inhibition as the mechanism of action has been proven in many cancers such as melanoma, lung cancer, head and neck cancer, urological tumors, and gastric cancer, and is also applicable to insurance in Japan. Clinical trials have shown that, regardless of the type of cancer, 10-20% of people can survive for a long time. In studies of lung cancer, this long-term survival rate of surviving more than 5 years without progression was reported even after treatment was completed within 2 years. Several biomarkers related to short-term response, such as tumor PD-L1 and tumor gene mutation amount, have been studied, but no biomarkers for predicting long-term survival have been studied so far. [0003] As a biomarker t...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/395G01N33/49G01N33/48G01N33/68A61K45/00A61P35/00A61P43/00C07K16/28C12Q1/02C12Q1/06
CPCA61P35/00A61P43/00G01N2800/52G01N2333/70514G01N2333/70517G01N33/5091G01N33/57492A61K2039/505C07K16/2818A61K45/06G01N33/50A61K35/17C07K14/70514C07K14/70564G01N33/57484
Inventor 各务博
Owner SAITAMA MEDICAL UNIVERSITY