Data from KLRG1 Cell Depletion as a Novel Therapeutic Strategy in Patients with Mature T-Cell Lymphoma Subtypes

• DOI: 10.1158/1078-0432.c.7265752
• Publication Date: 2024-06-03T07:31:10Z
• Authors: Bimarzhan Assatova; Robert Willim; Christopher Trevi...; Garrett Haskett; Khyati Maulik Kariya; Kusha Chopra; Sung Rye Park; Michael Yevgeniy ...; Sean M. McCabe; Jessica Duffy; Abner Louissaint; Jani Huuhtanen; Dipabarna Bhattac...; Satu Mustjoki; Min Jung Koh; Foster Powers; Elizabeth A. Morgan; Lei Yang; Brandy Pinckney; Matthew J. Cotton; Andrew Crabbe; Jessica Beth Ziemba; Ian Brain; Tayla B. Heavican...; Javeed Iqbal; Ronald Nemec; Anna Baird Rider; Josie Germain Ford; Min Ji Koh; Nora Scanlan; David J. Feith; Thomas P. Loughran; Won Seog Kim; Jaehyuk Choi; Juliette Roels; Lena Boehme; Tom Putteman; Tom Taghon; Jeffrey A. Barnes; P. Connor Johnson; Eric D. Jacobsen; Steven A. Greenberg; David M. Weinstock; Salvia Jain
• Keywords: T-Cell Lymphoma

<div>AbstractPurpose:<p>Develop a novel therapeutic strategy for patients with subtypes of mature T-cell and NK-cell neoplasms.</p>Experimental Design:<p>Primary specimens, cell lines, patient-derived xenograft models, commercially available, proprietary anti-KLRG1 antibodies were used screening, target, functional validation.</p>Results:<p>Here we demonstrate that surface KLRG1 is highly expressed on tumor cells in subsets extranodal NK/T-cell lymphoma (ENKTCL), T-prolymphocytic leukemia (T-PLL), gamma/delta (G/D TCL). The majority the CD8<sup>+</sup>/CD57<sup>+</sup> or CD3<sup>−</sup>/CD56<sup>+</sup> leukemic derived from T- NK-large granular lymphocytic (T-LGLL NK-LGLL), respectively, KLRG1. humanized afucosylated monoclonal antibody (mAb208) optimized mouse <i>in vivo</i> use depleted KLRG1<sup>+</sup> TCL by mechanisms ADCC, ADCP, CDC rather than apoptosis. mAb208 induced ADCC ADCP T-LGLL <i>ex vivo</i>. effected healthy donor-derived NK, CD4<sup>+</sup>, CD8<sup>+</sup> Tem, TemRA while sparing KLRG1<sup>−</sup> naïve Tcm cells. Treatment line xenografts anti-CD47 mAb alone combination PI3K-δ/γ inhibitor duvelisib extended survival. depletion macrophages antagonized efficacy.</p>Conclusions:<p>Our findings suggest potential benefit broader treatment combining PI3Ki neoplasms.</p><p><i><a href="https://aacrjournals.org/clincancerres/article/doi/10.1158/1078-0432.CCR-24-0374" target="_blank">See related commentary Varma Diefenbach, p. 2300</a></i></p></div>