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Use of anti-PD-1 antibody in treatment of tumors

A technology of PD-1 and antibody, which is applied in the field of melanoma and solid tumor treatment, and can solve problems such as poor efficacy

Active Publication Date: 2020-03-17
SHANGHAI JUNSHI BIOSCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Retrospective study by Cho, J. et al., Invest New Drugs (2016), 34:677-84 shows that immunotherapy is less effective in ALM and MM compared with CSD melanoma

Method used

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  • Use of anti-PD-1 antibody in treatment of tumors
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  • Use of anti-PD-1 antibody in treatment of tumors

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0191] Example 1: Clinical research on anti-PD-1 antibody monotherapy for tumor treatment

[0192] Inclusion Criteria: Eligible subjects must (1) be between the ages of 18 and 70, (2) have metastatic melanoma or urological cancer, (3) be refractory to standard systemic therapy, (4) ) ECOG score of 0 or 1, (5) no history of autoimmune disease or persistent infection, (6) not received any immunotherapy before.

[0193] Subjects must have evaluable lesions according to RECIST v 1.1 standards, and are not allowed to use anti-tumor drug therapy, systemic steroid drug therapy or have not used anti-CTLA4, anti-PD-1, anti-PD-L1 antibody therapy. The demographic data of the enrolled subjects are shown in Table 1.

[0194] Table 1: Demographic data of enrolled subjects

[0195]

[0196] Test drug: anti-PD-1 antibody toripalimab (WO2014206107).

[0197] There are three anti-PD-1 antibody dose groups in this trial, namely: 1mg / kg (n=15), 3mg / kg (n=15) and 10mg / kg (n=6), administered...

Embodiment 2

[0237] Example 2: Research on the correspondence between natural killer cells (NK) and anti-PD-1 antibody therapeutic effect on tumors

[0238] During the course of the clinical trial described in Example 1, the frequency and activation status (by CD45RA staining) of T lymphocytes in whole blood were assessed. Anti-PD-1 antibody against activated CD8 in the peripheral blood of a single subject + The frequency of T lymphocytes had little effect. Such as Figure 5 As shown, in the group with PFS greater than 250 days, CD8 + Subjects with high cell activation rates were enriched. Before toripalimab treatment, all subjects activated CD8 + The average percentage is 65%. 4 / 5 durable responders (PFS >300 days) were found to have more than 80% activated CD8 in peripheral blood + (total CD8 + cells) and more than 26% CD3 - CD16 + CD54 + NK cells (total monocytes); in contrast activated CD8 in all subjects + The average percentages of T cells and NK cells were 65% and 20%, re...

Embodiment 3

[0239] Example 3: Research on the correlation between biomarkers and clinical efficacy

[0240] By performing PD-L1CD8 double IHC staining on tumor biopsy specimens of 28 patients, the correlation between tumor histology and anti-PD-1 antibody clinical efficacy was analyzed. Rabbit anti-human PD-L1 antibody SP142 from Roche and anti-CD8 clone 4B11 were used. PD-L1 positive status was defined as the presence of ≥1% membrane staining intensity of tumor cells.

[0241] Such as Figure 6 and Figure 7 As shown, subjects with positive PD-L1 expression in tumor biopsies benefited more from TORIPALIMAB treatment than subjects with negative PD-L1 expression (43.8% ORR, 62.5 DCR vs. 0% ORR, 50% DCR) . The subpopulation with high PD-1 expression (>50%) responded best to TORIPALIMAB treatment, with an ORR of 57.1% and a DCR of 71.4%. Notably, all ORR (CR+PR) subjects were dual positive for PD-L1 and TIL. Co-localization of TILs and PD-L1+ cells was found in tumor biopsies, and 93.8...

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Abstract

The present invention relates to the use of an anti-PD-1 antibody in the treatment of tumors. The invention also relates to use of a reagent for detecting the state of CD8 + T cells and / or NK cells inperipheral blood or a reagent for detecting EMSY genes in a detection kit for predicting the treatment effect of a tumor patient on the anti-PD-1 antibody and / or an antigen binding fragment thereof.

Description

technical field [0001] The present invention relates to the use of anti-PD-1 antibody in treating tumors. Specifically, the present invention relates to the use of anti-PD-1 antibodies in the treatment of solid tumors, especially melanoma; and the use of anti-PD-1 antibodies in the preparation of drugs for the treatment of solid tumors, especially melanoma; and the use of biological A method for predicting the curative effect of an anti-PD-1 antibody in the treatment of a solid tumor by a marker; and the use of a combination therapy or composition comprising the anti-PD-1 antibody in the treatment of a solid tumor. Background technique [0002] Immune escape is one of the hallmarks of cancer. Ahmadzadeh, M. et al., Blood, 114:1537-44 disclosed that tumor-specific T lymphocytes often exist in the tumor microenvironment, draining lymph nodes and peripheral blood, but due to the immunosuppressive mechanism network existing in the tumor microenvironment, their Often the progre...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/395A61P35/00G01N33/574G01N33/577G01N33/68C12Q1/6886
CPCA61K45/06A61K2039/505A61P35/00A61K2039/876C07K16/2818
Inventor 姚盛冯辉武海
Owner SHANGHAI JUNSHI BIOSCI
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