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p95HER2-T cell bispecific antibody for breast cancer treatment.
Rius Ruiz, Irene; Vicario, Rocio; Morancho, Beatriz; Morales, Cristina Bernadó; Arenas, Enrique J; Herter, Sylvia; Freimoser-Grundschober, Anne; Somandin, Jitka; Sam, Johannes; Ast, Oliver; Barriocanal, Águeda Martinez; Luque, Antonio; Escorihuela, Marta; Varela, Ismael; Cuartas, Isabel; Nuciforo, Paolo; Fasani, Roberta; Peg, Vicente; Rubio, Isabel; Cortés, Javier; Serra, Violeta; Escriva-de-Romani, Santiago; Sperinde, Jeff; Chenna, Ahmed; Huang, Weidong; Winslow, John; Albanell, Joan; Seoane, Joan; Scaltriti, Maurizio; Baselga, Jose; Tabernero, Josep; Umana, Pablo; Bacac, Marina; Saura, Cristina; Klein, Christian; Arribas, Joaquín.
Afiliación
  • Rius Ruiz I; Preclinical Research Program, Vall d'Hebron Institute of Oncology (VHIO), 08035 Barcelona, Spain.
  • Vicario R; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), 08035 Barcelona, Spain.
  • Morancho B; Preclinical Research Program, Vall d'Hebron Institute of Oncology (VHIO), 08035 Barcelona, Spain.
  • Morales CB; Preclinical Research Program, Vall d'Hebron Institute of Oncology (VHIO), 08035 Barcelona, Spain.
  • Arenas EJ; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), 08035 Barcelona, Spain.
  • Herter S; Preclinical Research Program, Vall d'Hebron Institute of Oncology (VHIO), 08035 Barcelona, Spain.
  • Freimoser-Grundschober A; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), 08035 Barcelona, Spain.
  • Somandin J; Preclinical Research Program, Vall d'Hebron Institute of Oncology (VHIO), 08035 Barcelona, Spain.
  • Sam J; Roche Innovation Center Zurich, Roche Pharmaceutical Research and Early Development, Wagistrasse 18, 8952 Schlieren, Switzerland.
  • Ast O; Roche Innovation Center Zurich, Roche Pharmaceutical Research and Early Development, Wagistrasse 18, 8952 Schlieren, Switzerland.
  • Barriocanal ÁM; Roche Innovation Center Zurich, Roche Pharmaceutical Research and Early Development, Wagistrasse 18, 8952 Schlieren, Switzerland.
  • Luque A; Roche Innovation Center Zurich, Roche Pharmaceutical Research and Early Development, Wagistrasse 18, 8952 Schlieren, Switzerland.
  • Escorihuela M; Roche Innovation Center Zurich, Roche Pharmaceutical Research and Early Development, Wagistrasse 18, 8952 Schlieren, Switzerland.
  • Varela I; Preclinical Research Program, Vall d'Hebron Institute of Oncology (VHIO), 08035 Barcelona, Spain.
  • Cuartas I; Preclinical Research Program, Vall d'Hebron Institute of Oncology (VHIO), 08035 Barcelona, Spain.
  • Nuciforo P; Preclinical Research Program, Vall d'Hebron Institute of Oncology (VHIO), 08035 Barcelona, Spain.
  • Fasani R; Preclinical Research Program, Vall d'Hebron Institute of Oncology (VHIO), 08035 Barcelona, Spain.
  • Peg V; Translational Research Program, VHIO, 08035 Barcelona, Spain.
  • Rubio I; Clinical Research Program, VHIO, 08035 Barcelona, Spain.
  • Cortés J; Clinical Research Program, VHIO, 08035 Barcelona, Spain.
  • Serra V; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), 08035 Barcelona, Spain.
  • Escriva-de-Romani S; Vall d'Hebron University Hospital, 08035 Barcelona, Spain.
  • Sperinde J; Vall d'Hebron University Hospital, 08035 Barcelona, Spain.
  • Chenna A; Clinical Research Program, VHIO, 08035 Barcelona, Spain.
  • Huang W; Preclinical Research Program, Vall d'Hebron Institute of Oncology (VHIO), 08035 Barcelona, Spain.
  • Winslow J; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), 08035 Barcelona, Spain.
  • Albanell J; Clinical Research Program, VHIO, 08035 Barcelona, Spain.
  • Seoane J; Vall d'Hebron University Hospital, 08035 Barcelona, Spain.
  • Scaltriti M; Monogram Biosciences, Laboratory Corporation of America Holdings, South San Francisco, CA 94080, USA.
  • Baselga J; Monogram Biosciences, Laboratory Corporation of America Holdings, South San Francisco, CA 94080, USA.
  • Tabernero J; Monogram Biosciences, Laboratory Corporation of America Holdings, South San Francisco, CA 94080, USA.
  • Umana P; Monogram Biosciences, Laboratory Corporation of America Holdings, South San Francisco, CA 94080, USA.
  • Bacac M; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), 08035 Barcelona, Spain.
  • Saura C; Cancer Research Program, IMIM (Hospital del Mar Medical Research Institute), 08003 Barcelona, Spain.
  • Klein C; Medical Oncology Service, Hospital del Mar, 08003 Barcelona, Spain.
  • Arribas J; Universitat Pompeu Fabra, 08003 Barcelona, Spain.
Sci Transl Med ; 10(461)2018 10 03.
Article en En | MEDLINE | ID: mdl-30282693
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.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Linfocitos T / Anticuerpos Biespecíficos / Receptor ErbB-2 Límite: Animals / Female / Humans Idioma: En Revista: Sci Transl Med Asunto de la revista: CIENCIA / MEDICINA Año: 2018 Tipo del documento: Article País de afiliación: España Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Linfocitos T / Anticuerpos Biespecíficos / Receptor ErbB-2 Límite: Animals / Female / Humans Idioma: En Revista: Sci Transl Med Asunto de la revista: CIENCIA / MEDICINA Año: 2018 Tipo del documento: Article País de afiliación: España Pais de publicación: Estados Unidos