| Literature DB >> 30282693 |
Irene Rius Ruiz1,2, Rocio Vicario1, Beatriz Morancho1,2, Cristina Bernadó Morales1,2, Enrique J Arenas1, Sylvia Herter3, Anne Freimoser-Grundschober3, Jitka Somandin3, Johannes Sam3, Oliver Ast3, Águeda Martinez Barriocanal1, Antonio Luque1, Marta Escorihuela1, Ismael Varela1, Isabel Cuartas4, Paolo Nuciforo5, Roberta Fasani5, Vicente Peg2,6, Isabel Rubio6, Javier Cortés5, Violeta Serra1,2, Santiago Escriva-de-Romani5,6, Jeff Sperinde7, Ahmed Chenna7, Weidong Huang7, John Winslow7, Joan Albanell2,8,9,10, Joan Seoane2,4,11,12, Maurizio Scaltriti13, Jose Baselga14, Josep Tabernero2,5,6, Pablo Umana3, Marina Bacac3, Cristina Saura5,6, Christian Klein3, Joaquín Arribas15,2,11,12.
Abstract
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.Entities:
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Year: 2018 PMID： 30282693 PMCID： PMC6498439 DOI： 10.1126/scitranslmed.aat1445
Source DB: PubMed Journal: Sci Transl Med ISSN： 1946-6234 Impact factor: 17.956