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: 0088

Profound B Cell Depletion and Repopulation with Predominantly Naïve B Cells in Non-Human Primates Achieved Through a Novel In Vivo CD8-Targeted Lipid Nanoparticle mRNA CAR

Aric Frantz1, Romina Riener1, Annabel Wang1, Yanjie Bao1, Yan Zhang1, Daiki Matsuda1, John Li1, David Chu1, Theresa Hunter1, Qian Chen Yong1, Michelle Nguyen1, Stuart Sievers1, Duy Nguyen1, Scott Roberts1, Diana Galvan1, Jerel Boyd Vega1, Matthew Butcher1, Stanley Zhang1, Stephen Flynn1, Yi Kuo1, Steven Tanis1, John Scholler2, Gregor Adams1, Michael Rosenzweig1, Priya Karmali1, Adrian Bot1, Carl June2 and Haig Aghajanian1, 1Capstan Therapeutics, San Diego, CA, 2University of Pennsylvania Perelman School of Medicine, Philadelphia, PA

Meeting: ACR Convergence 2024

Keywords: Animal Model, autoimmune diseases, B-Lymphocyte, Myositis, 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: SLE – Animal Models Poster

Session Type: Poster Session A

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

Background/Purpose: Ex vivo chimeric antigen receptor (CAR) T cell therapies have revolutionized cancer treatment and are demonstrating durable clinical efficacy in various autoimmune disease indications. Despite the success of current CAR T therapies, challenges in cell manufacturing, scalability, utilization of integrating viral vectors, and the need for lymphodepleting chemotherapy highlight the necessity for an off-the-shelf in vivo CAR technology applicable for broader use. To that aim, we developed an in vivo anti-CD19 CAR mRNA product delivered by a CD8-targeted lipid nanoparticle (tLNP) (CPTX2309) and evaluated the activity of a cross reactive anti-CD20 CAR surrogate (CPTX2309-S) in non-human primates (NHPs).

Methods: Twenty cynomolgus macaques were intravenously administered escalating doses of CPTX2309-S, which showed comparable activity with CPTX2309 in vitro. A dose range of 0.1 – 1.5 mg/kg was evaluated for safety and tolerability, B cell depletion in blood and tissues, as well as B cell repopulation (0.3 – 1.5 mg/kg) using a compact dose regimen (3x q72hr). 

Results: CPTX2309-S administration resulted in robust, dose-dependent, and transient CAR T cell engineering in vivo, with CAR expression of up to 85% on CD8+ T cells and CD8+ natural killer (NK) cells. There was also CAR expression on monocytes, but minimal transfection of CD4+ T cells. CPTX2309-S had an excellent safety and tolerability profile at doses of 0.1 – 1.0 mg/kg x3 and led to rapid and complete depletion of peripheral blood B cells as early as 6 hours post first dose, even at 0.1 mg/kg. B cells in tissues were significantly reduced in a dose dependent manner upon analysis after the final dose, with comparable deep B cell depletion observed at doses of 0.5 mg/kg and above. B cell recovery started within 2-3 weeks after depletion, and the repopulating B cells were predominantly naive (CD27- IgD+), with very few post-switch memory B cells (CD27+ IgD-). This contrasts with the pre-dose condition, which featured a higher presence of switched memory B cells. This return of mostly naïve B cells paralleled the observation of returning B cells in reports of autoimmune disease patients treated with ex vivo CD19 CAR T cells (Müller, 2024), indicative of an ‘immune reset’.

Conclusion: CPTX2309 is a non-viral in vivo CAR therapy that brings together the unprecedented potency of CAR constructs with the scalability and feasibility of this novel tLNP-mRNA platform. CPTX2309-S rapidly and efficiently delivers a therapeutic anti-CD20 CAR mRNA payload to cynomolgus macaque effector T cells in vivo, resulting in highly functional CAR-engineered T cells and deep B cell depletion that is transient and featured returning cells that were predominantly of a naïve phenotype. These findings demonstrate the feasibility of this novel in vivo CAR technology and support its translation to clinic, highlighting the potential to reset the immune system in patients with B cell involved autoimmune diseases to achieve a durable, drug-free clinical response


Disclosures: A. Frantz: None; R. Riener: None; A. Wang: None; Y. Bao: None; Y. Zhang: None; D. Matsuda: None; J. Li: None; D. Chu: None; T. Hunter: None; Q. Yong: None; M. Nguyen: None; S. Sievers: None; D. Nguyen: None; S. Roberts: None; D. Galvan: None; J. Boyd Vega: None; M. Butcher: None; S. Zhang: None; S. Flynn: None; Y. Kuo: None; S. Tanis: None; J. Scholler: None; G. Adams: None; M. Rosenzweig: None; P. Karmali: None; A. Bot: None; C. June: Gilead, 10, Novartis, 10; H. Aghajanian: Pfizer, 6.

To cite this abstract in AMA style:

Frantz A, Riener R, Wang A, Bao Y, Zhang Y, Matsuda D, Li J, Chu D, Hunter T, Yong Q, Nguyen M, Sievers S, Nguyen D, Roberts S, Galvan D, Boyd Vega J, Butcher M, Zhang S, Flynn S, Kuo Y, Tanis S, Scholler J, Adams G, Rosenzweig M, Karmali P, Bot A, June C, Aghajanian H. Profound B Cell Depletion and Repopulation with Predominantly Naïve B Cells in Non-Human Primates Achieved Through a Novel In Vivo CD8-Targeted Lipid Nanoparticle mRNA CAR [abstract]. Arthritis Rheumatol. 2024; 76 (suppl 9). https://acrabstracts.org/abstract/profound-b-cell-depletion-and-repopulation-with-predominantly-naive-b-cells-in-non-human-primates-achieved-through-a-novel-in-vivo-cd8-targeted-lipid-nanoparticle-mrna-car/. 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/profound-b-cell-depletion-and-repopulation-with-predominantly-naive-b-cells-in-non-human-primates-achieved-through-a-novel-in-vivo-cd8-targeted-lipid-nanoparticle-mrna-car/

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