JNJ-78306358, a first-in-class bispecific T cell engaging antibody targeting CD3 and HLA-G

IF 4.6 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience Pub Date : 2025-02-04 DOI:10.1016/j.isci.2025.111876

Nataša Obermajer , Adam Zwolak , Kelly van de Ven , Shana Versmissen , Krista Menard , Katharine Rogers , Ted Petley , Dan Weinstock , Jason Aligo , Jaymala Patel , Ken Tian , Lorraine Angelillo , Fang Yi , Stephen Jarantow , Keith Schutsky , Yoshitomo Hamuro , Diana Alvarez Arias , Kristel Buyens , Tsun-Wen Sheena Yao , Vince Torti , Sylvie Laquerre

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引用次数: 0

Abstract

T cell-redirecting bispecific antibodies (bsAbs) to treat advanced stage solid tumors are gaining interest after recent clinical successes. The immune checkpoint human leukocyte antigen G (HLA-G) is expressed in several tumor types while in normal tissues expression is limited. Here, we describe JNJ-78306358, a T cell-redirecting bispecific antibody (bsAb) to treat advanced stage solid tumors. JNJ-78306358 binds with high affinity to the α3 subunit of HLA-G on cancer cells and with purposely engineered weaker affinity to CD3ε on T cells. JNJ-78306358 induced potent T cell-mediated cytotoxicity of HLA-G-expressing solid tumors in vitro and in vivo. JNJ-78306358 also blocked the interaction of HLA-G with its receptors in vitro, indicating that immune checkpoint blocking may contribute to its anti-tumor activity. These results suggest that T cell-redirection against HLA-G could be a potent and effective treatment for a wide range of solid tumor indications.

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来源期刊

iScience Multidisciplinary-Multidisciplinary

CiteScore

7.20

自引率

1.70%

发文量

1972

审稿时长

6 weeks

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