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Binding proteins specific for ha-1h and uses thereof

A protein-binding and specific technology, applied in peptide/protein components, animal/human proteins, immunoglobulin superfamily, etc., can solve the problems of lack of in vivo persistence of T cells and in vivo anti-leukemia reactivity

Pending Publication Date: 2021-07-30
ACADEMISCH ZIEKENHUIS BIJ DE UNIV VAN AMSTERDAM ACADEMISCH MEDISCH CENT
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, it has been previously shown in phase I clinical studies that in vitro cultured HA-1-specific T cells derived from donor T cell repertoires lack in vivo persistence and in vivo anti-leukemic reactivity (Meij et al., 2012)

Method used

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  • Binding proteins specific for ha-1h and uses thereof
  • Binding proteins specific for ha-1h and uses thereof
  • Binding proteins specific for ha-1h and uses thereof

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Embodiment

[0443] TCR gene transfer is an attractive strategy to modify T cells with well-defined specificities in a short period of time. Recently, the effectiveness of TCR transfer was demonstrated in melanoma or synoviocyte sarcoma patients treated with TCR-modified autologous T cells. In order to engineer T cells capable of selective GvL without GvHD, we prefer to transfer HA-1-TCR. To expand the applicability of acquired T cell therapy in hematological malignancies, we initiated a clinical study using HA-1-TCR-transferred virus-specific T cells. We sequenced the TCR chains of three HA-1-specific T cell clones, M2, M7 and FK47.83 (Table 4).

[0444]

[0445]

[0446] Table 4. HA-1-TCR sequences of clones M2, M7 and FK47.83.

[0447] As previously described, we again observed that all three HA-1-specific T cell clones expressed a β chain with a similar V region (TRBV7-9) (4). A LZRS retroviral construct encoding the TCR alpha and beta chains of M2 and M7 was prepa...

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Abstract

Novel nucleic acid compositions, vectors, modified cells and pharmaceutical compositions are provided that are useful for treating or preventing a relapse of a haematological malignancy after allogeneic stem cell transplantation (allo-SCT) in a HLA-A*0201 positive human subject. Corresponding methods and uses are also provided.

Description

technical field [0001] The present invention provides novel nucleic acid compositions, vector systems, modified cells and pharmaceutical compositions useful for the treatment or prevention of hematological disorders after allogeneic stem cell transplantation (allo-SCT) in HLA-A*0201-positive human subjects recurrence of malignancy. Corresponding methods and uses are also provided. Background technique [0002] Hematological malignancies are cancers that affect the blood and lymphatic system. Cancer may start in blood-forming tissues, such as the bone marrow, or in cells of the immune system. Patients with hematologic malignancies can be successfully treated with human leukocyte antigen (HLA)-matched allogeneic stem cell transplantation (allo-SCT). To reduce the development of graft-versus-host disease (GvHD), donor T cells can be depleted from stem cell grafts and preemptively readministered after allo-SCT. Although this two-step procedure of T-cell-depleted allo-SCT and...

Claims

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Application Information

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IPC IPC(8): C07K14/725C07K14/74A61K35/17C12N5/0783
CPCC07K14/7051C07K14/70539C12N5/0636A61K39/4632A61K39/4611A61K2239/48A61K39/4644A61K39/464838C12N15/85A61K48/00A61K38/00A61P35/00C12N2510/00A61K35/17
Inventor 米丽娅姆·H·M·海姆斯凯克J·H·弗雷德里克·福尔肯伯格
Owner ACADEMISCH ZIEKENHUIS BIJ DE UNIV VAN AMSTERDAM ACADEMISCH MEDISCH CENT
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