On April 4, 2023 Autolus Therapeutics plc (Nasdaq: AUTL), a clinical-stage biopharmaceutical company developing next-generation programmed T cell therapies, reported the publication of a paper in Molecular Therapy titled ‘Dual targeting of CD19 and CD22 against B-ALL using a novel high-sensitivity aCD22 CAR (Press release, Autolus, APR 4, 2023, View Source [SID1234629810]).
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While CD19 CAR T cell therapy has had remarkable success in the treatment of B-cell malignancy, a proportion of patients may relapse with CD19 negative escape. Relapses due to antigen escape are a common cause of treatment failure in pediatric B-ALL. A solution to this is the co-targeting of a 2nd B-lineage antigen. CD22 is expressed early in B-cell development up until plasma cell differentiation and is expressed broadly by B-cell malignancies. Co-targeting of CD19 and CD22 is challenging for two reasons. Firstly, CD22 is a difficult CAR target being bulky and expressed at low density. Secondly, the optimal way of designing a CAR T cell which targets two antigens simultaneously has not been established.
In this paper, the Autolus research team first develop a highly sensitive CD22 CAR which can recognize target antigen even if CD22 is expressed at low density. Secondly, they explore a co-transduction approach with the clinically proven Autolus CD19 CAR, Obecabtagene autoleucel (obe-cel). The advantage of a co-transduction approach is that expression of neither obe-cel nor the new CD22 CAR are perturbed. This new CD19/CD22 CAR T cell therapeutic (AUTO1/22) was found to be effective in a mouse model of B-Cell Acute Lymphoblastic Leukemia (B-ALL) with CD19 negative escape.
AUTO1/22 is currently being tested in a pediatric study of relapsed/remitting (r/r) B-ALL [NCT02443831].
"CD22 targeting and CD19/CD22 co-targeting are challenging technical problems in the field," said Martin Pule, Chief Scientific Officer, and Founder of Autolus. "Development of AUTO1/22 in this paper represents the state-of-the-art with a high-sensitivity CD22 receptor and efficient co-targeting."
"I am delighted to see publication of the pre-clinical data for AUTO1/22," added Christian Itin, Chief Executive Officer of Autolus. "This work builds on our success with CD19 targeting with obe-cel and represents a significant evolution of our obe-cel platform. AUTO1/22 may reduce CD19 negative escape in children with B-ALL and may have broader applications in improving outcomes in other B-cell malignancies."
1.Evangelia Kokalaki, Biao Ma, Mathieu Ferrari et al. Dual targeting of CD19 and CD22 against B-ALL using a novel high-sensitivity aCD22 CAR. Molecular Therapy. The full publication can be viewed here.