更新于：2024-11-01

HLA-A 24

更新于：2024-11-01

基本信息

别名-

简介-

关联

项与 HLA-A 24 相关的药物

Foxp3-#32

靶点

FOXP3 x HLA-A 24

作用机制

FOXP3调节剂 [+1]

在研机构

Eureka Therapeutics, Inc.

原研机构

Eureka Therapeutics, Inc.

在研适应症

肿瘤

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

Vbx-026

靶点

HER2 x HLA-A 24

作用机制

HER2调节剂 [+1]

在研机构

VAXON Biotech SA

原研机构

VAXON Biotech SA

在研适应症

肿瘤

非在研适应症-

最高研发阶段药物发现

首次获批国家/地区-

首次获批日期1800-01-20

UI-3

靶点

HLA-A 24 x MAGEA4

作用机制

HLA-A 24调节剂 [+1]

在研机构-

原研机构

United Immunity Co. Ltd.初创企业

在研适应症-

非在研适应症

头颈部肿瘤 [+2]

最高研发阶段终止

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 HLA-A 24 相关的临床结果

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100 项与 HLA-A 24 相关的转化医学

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0 项与 HLA-A 24 相关的专利（医药）

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301

项与 HLA-A 24 相关的文献（医药）

2024-12-01·Transplant Immunology

Donor-derived cytomegalovirus-specific CD8+ T cells restricted to shared, donor-specific, or host-specific HLA after HLA mismatched hematopoietic stem cell transplantation

Article

作者: Yoshihara, Kyoko ; Fujiwara, Hiroshi ; Fukunaga, Keiko ; Ikegame, Kazuhiro ; Osugi, Yuko ; Tamaki, Hiroya ; Kaida, Katsuji ; Okada, Masaya ; Teramoto, Masahiro ; Yoshihara, Satoshi ; Inoue, Takayuki

Immune reconstitution after human leukocyte antigen (HLA)-mismatched (haploidentical) hematopoietic stem cell transplantation (haplo-HCT) can significantly influence long-term outcomes. The three possible HLA haplotypes after transplantation are: one carried by both the patient and the donor (shared HLA), one by donor only (donor-specific HLA), and one by patient only (host-specific HLA), and the donor T cells remain restricted to one of these three haplotypes. Understanding the presence of donor T cells restricted to each haplotype may provide more detailed insights into post-transplant immune response and potentially provide valuable information for the development of chimeric antigen receptor T cell or T cell receptor T cell constructs. In this study, patients or donors with HLA-A24 or HLA-A2 were tested with HLA-A*24:02- and A*02:01-restricted cytomegalovirus (CMV)-specific tetramers for detecting the respective HLA-restricted T cells. Sixty-four samples from 40 patients were assayed. More than half of the patients at day 90 and all patients by day 900 had shared HLA-restricted T cells. After day 90, half of the patients had donor-specific HLA-restricted T cells, but no host-specific HLA-restricted T cells were found. In the comparative analysis of the transplant types, shared HLA-restricted T cells were positive in all three categories: haplo-HCT (50%), 2-haplo-mis-HCT (75%), and spousal HCT (67%). Furthermore, donor-specific HLA-restricted T cells demonstrated positivity in haplo-HCT at 57% and in 2-haplo-mis-HCT at 60%, with a threshold of 0.01%. Donor-specific HLA-restricted T cells for spousal HCT were not examined due to the lack of an appropriate HLA combination for the tetramers. The presence of shared HLA-restricted T cells explains the host defense after HLA-haploidentical transplantation, while the presence of donor-specific HLA-restricted T cells may account for host defense against hematotropic viruses, such as CMV. However, this study failed to detect host-specific HLA-restricted T cells, leaving the host defense against epitheliotropic viruses unresolved, thus requiring further investigation.

2024-10-01·HLA

Characterization of the Novel HLA‐A*24:02:169 Allele by Sequencing‐Based Typing

Article

作者: Cargou, Marine ; Elsermans, Vincent ; Labalette, Myriam ; Top, Isabelle ; Pajot, Thibault

ABSTRACTHLA‐A*24:02:169 differs from HLA‐A*24:02:01:01 by one nucleotide substitution in codon −23 in exon 1.

2024-10-01·Journal for ImmunoTherapy of Cancer

Dendritic cells pulsed with multifunctional Wilms’ tumor 1 (WT1) peptides combined with multiagent chemotherapy modulate the tumor microenvironment and enable conversion surgery in pancreatic cancer

Article

作者: Shimodaira, Shigetaka ; Koido, Shigeo ; Yanagisawa, Hiroyuki ; Suka, Machi ; Sugiyama, Haruo ; Sato, Nobuhiro ; Tsukinaga, Shintaro ; Ito, Zensho ; Kan, Shin ; Bito, Tuuse ; Shimabuku, Masamori ; Uchiyama, Kan ; Ohkusa, Toshifumi ; Taguchi, Junichi ; Saruta, Masayuki ; Misawa, Takeyuki

BackgroundWe aimed to develop a chemoimmunotherapy regimen consisting of a novel Wilms’ tumor 1 (WT1) peptide-pulsed dendritic cell (WT1-DC) vaccine and multiagent chemotherapy and to investigate the safety, clinical outcomes, and WT1-specific immune responses of patients with unresectable advanced pancreatic ductal adenocarcinoma (UR-PDAC) who received this treatment.MethodsPatients with UR-PDAC with stage III disease (locally advanced (LA-PDAC; n=6)), stage IV disease (metastatic (M-PDAC; n=3)), or recurrent disease after surgery (n=1) were enrolled in this phase I study. The patients received one cycle of nab-paclitaxel plus gemcitabine alone followed by 15 doses of the WT1-DC vaccine independent of chemotherapy. The novel WT1 peptide cocktail was composed of a multifunctional helper peptide specific for major histocompatibility complex class II, human leukocyte antigen (HLA)-A*02:01, or HLA-A*02:06 and a killer peptide specific for HLA-A*24:02.ResultsThe chemoimmunotherapy regimen was well tolerated. In the nine patients for whom a prognostic analysis was feasible, the clinical outcomes of long-term WT1 peptide-specific delayed-type hypersensitivity (WT1-DTH)-positive patients (n=4) were significantly superior to those of short-term WT1-DTH-positive patients (n=5). During chemoimmunotherapy, eight patients were deemed eligible for conversion surgery and underwent R0 resection (four patients with LA-PDAC, one patient with M-PDAC, and one recurrence) or R1 resection (one patient with M-PDAC), and one patient with LA-PDAC was determined to be unresectable. Long-term WT1-DTH positivity was observed in three of the four patients with R0-resected LA-PDAC. These three patients exhibited notable infiltration of T cells and programmed cell death protein-1+ cells within the pancreatic tumor microenvironment (TME). All patients with long-term WT1-DTH positivity were alive for at least 4.5 years after starting therapy. In patients with long-term WT1-DTH positivity, the percentage of WT1-specific circulating CD4+ or CD8+ T cells that produced IFN-γ or TNF-α was significantly greater than that in patients with short-term WT1-DTH positivity after two vaccinations. Moreover, after 12 vaccinations, the percentages of both circulating regulatory T cells and myeloid-derived suppressor cells were significantly lower in patients with long-term WT1-DTH-positive PDAC than in short-term WT1-DTH-positive patients.ConclusionsPotent activation of WT1-specific immune responses through a combination chemoimmunotherapy regimen including the WT1-DC vaccine in patients with UR-PDAC may modulate the TME and enable conversion surgery, resulting in clinical benefits (Online supplemental file 1).Trial registration numberjRCTc030190195.