ACR Meeting Abstracts

ACR Meeting Abstracts

  • Meetings
    • ACR Convergence 2024
    • ACR Convergence 2023
    • 2023 ACR/ARP PRSYM
    • ACR Convergence 2022
    • ACR Convergence 2021
    • ACR Convergence 2020
    • 2020 ACR/ARP PRSYM
    • 2019 ACR/ARP Annual Meeting
    • 2018-2009 Meetings
    • Download Abstracts
  • Keyword Index
  • Advanced Search
  • Your Favorites
    • Favorites
    • Login
    • View and print all favorites
    • Clear all your favorites
  • ACR Meetings

Abstract Number: 0002

Preclinical Evaluation of BCMA And/or CD19 Nanobody-based Single or Compound CAR-T Cells Targeting B and Plasma Cells Associated with Autoimmune Disorders

Byeong Hyeok Choi1, Vincent M DeStefano2, Masayuki Wada2, Kevin G Pinz1, Greg Deener2, Nabil Hagag1, Ahmed Abdel-Razek1, Yu Ma3, Jing Luo3 and Yupo Ma2, 1iCell Gene Therapeutics Inc., Stony Brook, NY, 2iCell Gene Therapeutics, Inc., Stony Brook, NY, 3iCar Bio Therapeutics Ltd, Zhongshan City, Guangdong, China (People's Republic)

Meeting: ACR Convergence 2024

Keywords: autoimmune diseases, B-Cell Targets, gene therapy, Lupus nephritis, Systemic lupus erythematosus (SLE)

  • Tweet
  • Click to email a link to a friend (Opens in new window) Email
  • Click to print (Opens in new window) Print
Session Information

Date: Saturday, November 16, 2024

Title: B Cell Biology & Targets in Autoimmune & Inflammatory Disease Poster

Session Type: Poster Session A

Session Time: 10:30AM-12:30PM

Background/Purpose: CD19 single and BCMA-CD19 compound chimeric antigen receptor (CAR) T cell therapy has demonstrated remarkable activity against autoimmune disorders, although relapses with CD19 CAR are reported. However, such CARs rely on classical single-chain fragment variable (scFv) with light and heavy chains connected by a peptide linker. This linker may induce immunogenicity in humans. FDA approved CD19 CAR uses the murine derived scFv FMC63 clone which has demonstrated induction of neutralizing antibodies against the CAR after infusion, impairing the potential to re-dose the patient. Additionally, the scFv structure may exhibit instability when binding to the antigen, and result in T cell exhaustion. To address such limitations, this study aimed to produce a novel CAR construct utilizing camelid-derived nanobodies that target both B and plasma cells.

Nanobodies derived from the variable heavy-chain (VHH) of camelid antibodies, naturally lack the light chain structure, and thus, the use of immunogenic peptide linker is not required. Their smaller size and greater stability make them ideal for constructing more complex CARs. Furthermore, nanobodies exhibit a high homology with the human immunoglobulins. Unlike scFvs, nanobodies do not induce neutralizing antibodies. To date, this is the first investigation of the pre-clinical efficacy of BCMA-CD19 nanobody-based CAR T cells in vitro and in vivo.

Methods: Alpacas were immunized with human BCMA or CD19 protein. Peripheral blood mononuclear cell (PBMC) mRNA was isolated and processed into a VHH gene library, transformed into phage-competent bacteria to generate a bacteriophage library. This library was panned against BCMA or CD19 antigens to enrich for binding clones, identified by high-throughput ELISA and cellular binding by flow cytometry. VHH candidates with binding greater than two-fold above background were sequenced. Using Biolayer Interferometry (BLI), association and dissociation rates were determined. Selected nanobodies were used to create a novel construct, termed BCMA-CD19 nanobody compound CAR (ncCAR). Human T cells were transduced with ncCAR and evaluated for cytotoxic efficacy through co-culture with BCMA or CD19-positive cell line. ncCAR cell-mediated cytotoxicity was assessed via flow cytometry and cell viability assays. In vivo studies were conducted using NSG (NOD scid gamma) mouse models engrafted with target cells, followed by infusion of ncCAR.

Results: Single nano-CARs (nCAR) and ncCAR demonstrated potent and selective cytotoxicity against BCMA or CD19-positive cells in vitro. Co-culture assays revealed significant BCMA or CD19 positive cell lysis, indicating effective dual-antigen targeting. In mouse models, both nCAR and ncCAR showed substantial cytotoxic activity, with depletion of BCMA and CD19 positive cells and significant durable persistency.

Conclusion: nCAR and ncCAR represents a promising therapeutic strategy for patients with autoimmune diseases who relapse after CAR therapy. The novel construct may provide improved efficacy and potential to re-dose a CAR relapsed patient. Future clinical studies are needed to explore this possibility in treating autoimmune disorders.


Disclosures: B. Choi: iCell Gene Therapeutics Inc., 3; V. DeStefano: iCell Gene Therapeutics, Inc., 3; M. Wada: iCell Gene Therapeutics, Inc., 3; K. Pinz: iCell Gene Therapeutics Inc., 3; G. Deener: iCell Gene Therapeutics, Inc., 4; N. Hagag: iCell Gene Therapeutics Inc., 3; A. Abdel-Razek: iCell Gene Therapeutics Inc., 3; Y. Ma: iCar Bio Therapeutics Ltd, 3; J. Luo: iCar Bio Therapeutics Ltd, 3; Y. Ma: iCell Gene Therapeutics, Inc., 4.

To cite this abstract in AMA style:

Choi B, DeStefano V, Wada M, Pinz K, Deener G, Hagag N, Abdel-Razek A, Ma Y, Luo J, Ma Y. Preclinical Evaluation of BCMA And/or CD19 Nanobody-based Single or Compound CAR-T Cells Targeting B and Plasma Cells Associated with Autoimmune Disorders [abstract]. Arthritis Rheumatol. 2024; 76 (suppl 9). https://acrabstracts.org/abstract/preclinical-evaluation-of-bcma-and-or-cd19-nanobody-based-single-or-compound-car-t-cells-targeting-b-and-plasma-cells-associated-with-autoimmune-disorders/. Accessed .
  • Tweet
  • Click to email a link to a friend (Opens in new window) Email
  • Click to print (Opens in new window) Print

« Back to ACR Convergence 2024

ACR Meeting Abstracts - https://acrabstracts.org/abstract/preclinical-evaluation-of-bcma-and-or-cd19-nanobody-based-single-or-compound-car-t-cells-targeting-b-and-plasma-cells-associated-with-autoimmune-disorders/

Advanced Search

Your Favorites

You can save and print a list of your favorite abstracts during your browser session by clicking the “Favorite” button at the bottom of any abstract. View your favorites »

All abstracts accepted to ACR Convergence are under media embargo once the ACR has notified presenters of their abstract’s acceptance. They may be presented at other meetings or published as manuscripts after this time but should not be discussed in non-scholarly venues or outlets. The following embargo policies are strictly enforced by the ACR.

Accepted abstracts are made available to the public online in advance of the meeting and are published in a special online supplement of our scientific journal, Arthritis & Rheumatology. Information contained in those abstracts may not be released until the abstracts appear online. In an exception to the media embargo, academic institutions, private organizations, and companies with products whose value may be influenced by information contained in an abstract may issue a press release to coincide with the availability of an ACR abstract on the ACR website. However, the ACR continues to require that information that goes beyond that contained in the abstract (e.g., discussion of the abstract done as part of editorial news coverage) is under media embargo until 10:00 AM ET on November 14, 2024. Journalists with access to embargoed information cannot release articles or editorial news coverage before this time. Editorial news coverage is considered original articles/videos developed by employed journalists to report facts, commentary, and subject matter expert quotes in a narrative form using a variety of sources (e.g., research, announcements, press releases, events, etc.).

Violation of this policy may result in the abstract being withdrawn from the meeting and other measures deemed appropriate. Authors are responsible for notifying colleagues, institutions, communications firms, and all other stakeholders related to the development or promotion of the abstract about this policy. If you have questions about the ACR abstract embargo policy, please contact ACR abstracts staff at [email protected].

Wiley

  • Online Journal
  • Privacy Policy
  • Permissions Policies
  • Cookie Preferences

© Copyright 2025 American College of Rheumatology