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 Cortés; Violeta 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

doi:10.1126/scitranslmed.aat1445

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

Department of Medicine

Research output: Contribution to journal › Article › Research

46 Citations (Scopus)

Abstract

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 language	English
Article number	eaat1445
Journal	Science Translational Medicine
Volume	10
DOIs	https://doi.org/10.1126/scitranslmed.aat1445
Publication status	Published - 3 Oct 2018

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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., ... Arribas, J. (2018). P95HER2–T cell bispecific antibody for breast cancer treatment. Science Translational Medicine, 10, [eaat1445]. https://doi.org/10.1126/scitranslmed.aat1445

@article{720c1d05ffcf45299f6a3739e8438c26,

title = "P95HER2–T cell bispecific antibody for breast cancer treatment",

abstract = "Copyright {\textcopyright} 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.",

author = "Ruiz, {Irene Rius} and Rocio Vicario and Beatriz Morancho and Morales, {Cristina Bernad{\'o}} and Arenas, {Enrique J.} and Sylvia Herter and Anne Freimoser-Grundschober and Jitka Somandin and Johannes Sam and Oliver Ast and Barriocanal, {{\'A}gueda Martinez} and Antonio Luque and Marta Escorihuela and Ismael Varela and Isabel Cuartas and Paolo Nuciforo and Roberta Fasani and Vicente Peg and Isabel Rubio and Javier Cort{\'e}s and Violeta Serra and Santiago Escriva-de-Romani and Jeff Sperinde and Ahmed Chenna and Weidong Huang and John Winslow and Joan Albanell and Joan Seoane and Maurizio Scaltriti and Jose Baselga and Josep Tabernero and Pablo Umana and Marina Bacac and Cristina Saura and Christian Klein and Joaqu{\'i}n Arribas",

year = "2018",

month = oct,

day = "3",

doi = "10.1126/scitranslmed.aat1445",

language = "English",

volume = "10",

journal = "Science Translational Medicine",

issn = "1946-6234",

publisher = "American Association for the Advancement of Science",

}

Ruiz, IR, Vicario, R, Morancho, B, Morales, CB, Arenas, EJ, Herter, S, Freimoser-Grundschober, A, Somandin, J, Sam, J, Ast, O, Barriocanal, ÁM, 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 2018, 'P95HER2–T cell bispecific antibody for breast cancer treatment', Science Translational Medicine, vol. 10, eaat1445. https://doi.org/10.1126/scitranslmed.aat1445

TY - JOUR

T1 - P95HER2–T cell bispecific antibody for breast cancer treatment

AU - Ruiz, Irene Rius

AU - Vicario, Rocio

AU - Morancho, Beatriz

AU - Morales, Cristina Bernadó

AU - Arenas, Enrique J.

AU - Herter, Sylvia

AU - Freimoser-Grundschober, Anne

AU - Somandin, Jitka

AU - Sam, Johannes

AU - Ast, Oliver

AU - Barriocanal, Águeda Martinez

AU - Luque, Antonio

AU - Escorihuela, Marta

AU - Varela, Ismael

AU - Cuartas, Isabel

AU - Nuciforo, Paolo

AU - Fasani, Roberta

AU - Peg, Vicente

AU - Rubio, Isabel

AU - Cortés, Javier

AU - Serra, Violeta

AU - Escriva-de-Romani, Santiago

AU - Sperinde, Jeff

AU - Chenna, Ahmed

AU - Huang, Weidong

AU - Winslow, John

AU - Albanell, Joan

AU - Seoane, Joan

AU - Scaltriti, Maurizio

AU - Baselga, Jose

AU - Tabernero, Josep

AU - Umana, Pablo

AU - Bacac, Marina

AU - Saura, Cristina

AU - Klein, Christian

AU - Arribas, Joaquín

PY - 2018/10/3

Y1 - 2018/10/3

N2 - 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.

AB - 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.

U2 - 10.1126/scitranslmed.aat1445

DO - 10.1126/scitranslmed.aat1445

M3 - Article

C2 - 30282693

SN - 1946-6234

VL - 10

JO - Science Translational Medicine

JF - Science Translational Medicine

M1 - eaat1445

ER -

P95HER2–T cell bispecific antibody for breast cancer treatment

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