JNJ-78306358, a first-in-class bispecific T cell engaging antibody targeting CD3 and HLA-G
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 <i>in vitro</i> and <i>in vivo</i>. JNJ-78306358 also blocked the interaction of HLA-G with its receptors <i>in vitro</i>, 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.
Authors
- Maté Ongenaert (ORCID: https://orcid.org/0000-0001-7520-871X)
- Dirk Brehmer
- Yi Fang (ORCID: https://orcid.org/0000-0001-7964-8018)
- Stephen Jarantow
- Krista Menard (ORCID: https://orcid.org/0000-0001-6114-5340)
- Kathryn Packman (ORCID: https://orcid.org/0000-0002-2686-6481)
- Aleksandra Brajic (ORCID: https://orcid.org/0000-0002-2598-3002)
- Marjolein van Heerden (ORCID: https://orcid.org/0000-0002-0852-092X)
- Julien Häsler
- Tsun-Wen Sheena Yao
- Jason Aligo (ORCID: https://orcid.org/0000-0002-1351-3994)
- Sanjaya Singh (ORCID: https://orcid.org/0000-0002-9119-7966)
- Lorraine Angelillo
- Kelly Van De Ven
- Katharine M. Rogers
- Josh Lauring (ORCID: https://orcid.org/0000-0002-4312-704X)
- Ken Tian
- Keith Schutsky
- Sylvie Laquerre
- Dan Weinstock
- Bie Verbist
- Brian Geist (ORCID: https://orcid.org/0009-0000-2199-732X)
- Ted Petley
- Regina J. Brown (ORCID: https://orcid.org/0000-0001-7715-1059)
- Diana Alvarez Arias
- Adam Zwolak (ORCID: https://orcid.org/0000-0001-6861-9078)
- Laurie Lenox (ORCID: https://orcid.org/0009-0001-1533-9838)
- Vince R. Torti
- Jacalyn S. Clawson
- Kristel Buyens
- Yoshitomo Hamuro (ORCID: https://orcid.org/0000-0001-8564-4718)
- Jacintha Shenton
- Jaymala Patel (ORCID: https://orcid.org/0000-0002-0232-2260)
- Matthew V. Lorenzi
- Shana Versmissen
- Nataša Obermajer (ORCID: https://orcid.org/0000-0002-0838-7508)
- James Greger (ORCID: https://orcid.org/0009-0006-5445-5723)
- Gerald Chu (ORCID: https://orcid.org/0009-0008-6407-8057)
Institutions
- Johnson & Johnson (United States) (US)
- Johnson & Johnson (Brazil) (BR)
Publication Details
- Journal
- iScience
- Published
- 2025-02-04
- DOI
- https://doi.org/10.1016/j.isci.2025.111876
- Citations
- 4
- Primary Topic
- Immune Cell Function and Interaction
- Type
- article
- Field-Weighted Citation Impact
- 3.19
Funders
- Janssen Research and Development