P95HER2–T cell bispecific antibody for breast cancer treatment

Irene Rius Ruiz, Rocio Vicario, Beatriz Morancho, Cristina Bernadó Morales, Enrique J. Arenas, Sylvia Herter, Anne Freimoser-Grundschober, Jitka Somandin, Johannes Sam, Oliver Ast, Águeda Martinez Barriocanal, Antonio Luque, Marta Escorihuela, Ismael Varela, Isabel Cuartas, Paolo Nuciforo, Roberta Fasani, Vicente Peg, Isabel Rubio, Javier CortésVioleta Serra, Santiago Escriva-de-Romani, Jeff Sperinde, Ahmed Chenna, Weidong Huang, John Winslow, Joan Albanell, Joan Seoane, Maurizio Scaltriti, Jose Baselga, Josep Tabernero, Pablo Umana, Marina Bacac, Cristina Saura, Christian Klein, Joaquín Arribas

Research output: Contribution to journalArticleResearch

46 Citations (Scopus)


Copyright © 2018 The Authors, some rights reserved. T cell bispecific antibodies (TCBs) are engineered molecules that include, within a single entity, binding sites to the T cell receptor and to tumor-associated or tumor-specific antigens. The receptor tyrosine kinase HER2 is a tumor-associated antigen in ~25% of breast cancers. TCBs targeting HER2 may result in severe toxicities, likely due to the expression of HER2 in normal epithelia. About 40% of HER2-positive tumors express p95HER2, a carboxyl-terminal fragment of HER2. Using specific antibodies, here, we show that p95HER2 is not expressed in normal tissues. We describe the development of p95HER2-TCB and show that it has a potent antitumor effect on p95HER2-expressing breast primary cancers and brain lesions. In contrast with a TCB targeting HER2, p95HER2-TCB has no effect on nontransformed cells that do not overexpress HER2. These data pave the way for the safe treatment of a subgroup of HER2-positive tumors by targeting a tumor-specific antigen.
Original languageEnglish
Article numbereaat1445
JournalScience Translational Medicine
Publication statusPublished - 3 Oct 2018


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