Diabetes and other autoimmune endocrine diseases

Poster

Using Antigen Specific Chimeric Antigen Receptor [car]-redirected T Cells to Remodel Immune Balance in Type 1 Diabetes

Friday, June 16
6:15 PM - 7:30 PM

Previously we showed that an insulin B:9-23 register 3 specific monoclonal antibody (mAb287) delayed spontaneous type 1 diabetes (T1D) when administrated to NOD mice. Of note, mAb287 delayed progression to overt hyperglycemia even when administrated at a late pre-diabetic stage. Efficacy was associated with a decrease in islet infiltration of lymphocytes suggesting that mAb287 is acting to delete and/or reprogram antigen presenting cells expressing the cognate peptide:MHC complex. The recent successes of chimeric antigen receptor (CAR)-redirected CD8 T cells in cancer immunotherapy prompted us to investigate whether the efficacy of this monoclonal antibody therapy could be enhanced by delivery in a cellular format. Accordingly, we now describe our results using mAb287-CAR CD8 T cells and control CAR-T cells.


Using our optimized protocol, up to 35% of activated CD8 T cells can be transduced with mAb287-CAR retroviruses. In vitro stimulation experiments confirm that mAb287-CAR-CD8 cells maintain the antigen binding specificity of the parent antibody, secreting IFNg in a dose dependent manner in response to insulin B:9-23(R3)/I-Ag7 complexes, but not controls.  Similarly, mAb287-CAR-CD8 T cells delete antigen presenting cells with the target antigen on their surface in vitro. Following adoptive transfer to young NOD mice GFP expressing mAb287-CAR-CD8 T cells could be detected by flow cytometry at least 2 weeks post-transfer in the spleens and lymph nodes. Recipient animals showed no evidence of acute toxicity following transfer. We propose that the antigen specific mAb redirected CAR T cells may be a safe immune therapy to arrest the progression of autoimmune diabetes.

LI ZHANG

Assistant Professor
Baylor College of Medicine

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    Tomasz Sosinowski

    University of Colorado

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      Sachin L. Badole

      Baylor College of Medicine

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        Nitin S. Sekhar

        Baylor College of Medicine

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          Massimo Pietropaolo

          Baylor College of Medicine

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            Howard W. Davidson

            University of Colorado

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