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Antibody Conditioning Enables MHC-Mismatched Hematopoietic Stem Cell Transplants and Organ Graft Tolerance.

Benson M George | Kevin S Kao | Hye-Sook Kwon | Brenda J Velasco | Jessica Poyser | Angela Chen | Alan C Le | Akanksha Chhabra | Cassandra E Burnett | Devon Cajuste | Malachia Hoover | Kyle M Loh | Judith A Shizuru | Irving L Weissman
Cell stem cell | 2019

Hematopoietic cell transplantation can correct hematological and immunological disorders by replacing a diseased blood system with a healthy one, but this currently requires depleting a patient's existing hematopoietic system with toxic and non-specific chemotherapy, radiation, or both. Here we report an antibody-based conditioning protocol with reduced toxicity and enhanced specificity for robust hematopoietic stem cell (HSC) transplantation and engraftment in recipient mice. Host pre-treatment with six monoclonal antibodies targeting CD47, T cells, NK cells, and HSCs followed by donor HSC transplantation enabled stable hematopoietic system reconstitution in recipients with mismatches at half (haploidentical) or all major histocompatibility complex (MHC) genes. This approach allowed tolerance to heart tissue from HSC donor strains in haploidentical recipients, showing potential applications for solid organ transplantation without immune suppression. Fully mismatched chimeric mice developed antibody responses to nominal antigens, showing preserved functional immunity. These findings suggest approaches for transplanting immunologically mismatched HSCs and solid organs with limited toxicity.

Pubmed ID: 31204177

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Associated grants

  • Agency: NCI NIH HHS, United States
    Id: R35 CA220434
  • Agency: NCI NIH HHS, United States
    Id: T32 CA009302
  • Agency: NIH HHS, United States
    Id: DP5 OD024558
  • Agency: NIGMS NIH HHS, United States
    Id: T32 GM119995
  • Agency: NIDDK NIH HHS, United States
    Id: R01 DK115600

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InVivoPlus anti-mouse CD154 (CD40L) (antibody)

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PE anti-mouse CD3 (antibody)

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APC anti-mouse TCR Vbeta6 (antibody)

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anti-mouse CD4 (antibody)

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InVivoPlus anti-mouse CD8α (antibody)

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InVivoMAb anti-mouse CD122 (IL-2Rβ) (antibody)

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InVivoMAb anti-mouse c-Kit (CD117) (antibody)

RRID:AB_2687818

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CB6F1/J (organism)

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Mus musculus with name CB6F1/J from IMSR.

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