P95HER2–T cell bispecific antibody for breast cancer treatment Journal Article
| Authors: | Ruiz, I. R.; Vicario, R.; Morancho, B.; Morales, C. B.; Arenas, E. J.; Herter, S.; Freimoser-Grundschober, A.; Somandin, J.; Sam, J.; Ast, O.; Barriocanal, Á M.; Luque, A.; Escorihuela, M.; Varela, I.; Cuartas, I.; Nuciforo, P.; Fasani, R.; Peg, V.; Rubio, I.; Cortés, J.; Serra, V.; Escriva-de-Romani, S.; Sperinde, J.; Chenna, A.; Huang, W.; Winslow, J.; Albanell, J.; Seoane, J.; Scaltriti, M.; Baselga, J.; Tabernero, J.; Umana, P.; Bacac, M.; Saura, C.; Klein, C.; Arribas, J. |
| Article Title: | P95HER2–T cell bispecific antibody for breast cancer treatment |
| 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. Copyright © 2018 The Authors, some rights reserved. |
| Journal Title: | Science Translational Medicine |
| Volume: | 10 |
| Issue: | 461 |
| ISSN: | 1946-6234 |
| Publisher: | American Association for the Advancement of Science |
| Date Published: | 2018-10-03 |
| Start Page: | eaat1445 |
| Language: | English |
| DOI: | 10.1126/scitranslmed.aat1445 |
| PUBMED: | 30282693 |
| PROVIDER: | scopus |
| PMCID: | PMC6498439 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 November 2018 -- Source: Scopus |
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