T-cell Activating Tribodies as a Novel Approach for Efficient Killing of ErbB2-positive Cancer Cells

Gennaro Riccio; Ana Rita Ricardo; Margherita Passariello; Kathy Saraiva; Valentina Rubino; Philip Cunnah; Nico Mertens; Claudia De Lorenzo

doi:10.1097/CJI.0000000000000248

T-cell Activating Tribodies as a Novel Approach for Efficient Killing of ErbB2-positive Cancer Cells

Gennaro Riccio
, Ana Rita Ricardo
, Margherita Passariello
, Kathy Saraiva
, Valentina Rubino
, Philip Cunnah
, Nico Mertens
, Claudia De Lorenzo

Risultato della ricerca: Contributo su rivista › Articolo in rivista › peer review

Abstract

L'articolo affronta uno dei profili più problematici della c.d. "saga Taricco", ossia dell'insieme delle sentenze e ordinanze scaturite a seguito della prima sentenza della Corte di giustizia UE nel 2015, C-105/14, Ivo Taricco et al.: viene dapprima esposto l'approccio adottato dalla Corte Costituzionale italiana e quello della Corte di giustizia Ue, mettendo in evidenza la diversità di impostazione teorica e le ricadute pratiche di ciascun criterio di interpretazione del rapporto fra primato, diritti fondamentali della persona e controlimiti costituzionali. Infine viene indicata una possibile chiave di lettura intermedia che potrebbe evitare in futuro il riaccendersi di conflittualità su vicende analoghe.

Lingua originale	Inglese
pagine (da-a)	1-10
Numero di pagine	10
Rivista	Journal of Immunotherapy
Volume	42
Numero di pubblicazione	1
DOI	https://doi.org/10.1097/CJI.0000000000000248
Stato di pubblicazione	Pubblicato - 1 gen 2019
Pubblicato esternamente	Sì

OSS delle Nazioni Unite

Questo processo contribuisce al raggiungimento dei seguenti obiettivi di sviluppo sostenibile

SDG 3 Salute e benessere

Accesso al documento

10.1097/CJI.0000000000000248

Altri file e collegamenti

Link to publication in Scopus

Cita questo

@article{8d8c7aa383824c82a48b0f31e63a2d01,

title = "T-cell Activating Tribodies as a Novel Approach for Efficient Killing of ErbB2-positive Cancer Cells",

abstract = "The Tyrosine Kinase Receptor ErbB2 (HER2) when overexpressed in breast cancer (BC) is associated with poor prognosis. The monoclonal antibody Trastuzumab has become a standard treatment of ErbB2+BC. The antibody treatment has limited efficacy, often meets resistance and induces cardiotoxicity. T-cell recruiting bispecific antibody derivatives (TRBA) offer a more effective alternative to standard antibody therapy. We evaluated a panel of TRBAs targeting 3 different epitopes on the ErbB2 receptor either in a bivalent targeting tribody structure or as a monovalent scFv-fusion (BiTE format) for binding, cytotoxicity on Trastuzumab-resistant cell lines, and induction of cardiotoxicity. All three TRBAs bind with high affinity to the ErbB2 extracellular domain and a large panel of ErbB2-positive tumor cells. Tribodies had an increased in vitro cytotoxic potency as compared to BiTEs. It is interesting to note that, Tribodies targeting the epitopes on ErbB2 receptor domains I and II bind and activate lysis of mammary and gastric tumor cells more efficiently than a Tribody targeting the Trastuzumab epitope on domain IV. The first 2 are also active on Trastuzumab-resistant cancer cells lacking or masking the epitope recognized by Trastuzumab. None of the Tribodies studied showed significant toxicity on human cardiomyocytes. Altogether these results make these novel anti-ErbB2 bispecific Tribodies candidates for therapeutic development for treating ErbB2-positive Trastuzumab-resistant cancer patients.",

keywords = "ErbB2/HER2, T-cell engager, cancer, immunotherapy, tribody",

author = "Gennaro Riccio and Ricardo, \{Ana Rita\} and Margherita Passariello and Kathy Saraiva and Valentina Rubino and Philip Cunnah and Nico Mertens and \{De Lorenzo\}, Claudia",

year = "2019",

month = jan,

day = "1",

doi = "10.1097/CJI.0000000000000248",

language = "English",

volume = "42",

pages = "1--10",

journal = "Journal of Immunotherapy",

issn = "1524-9557",

publisher = "Lippincott Williams and Wilkins",

number = "1",

}

TY - JOUR

T1 - T-cell Activating Tribodies as a Novel Approach for Efficient Killing of ErbB2-positive Cancer Cells

AU - Riccio, Gennaro

AU - Ricardo, Ana Rita

AU - Passariello, Margherita

AU - Saraiva, Kathy

AU - Rubino, Valentina

AU - Cunnah, Philip

AU - Mertens, Nico

AU - De Lorenzo, Claudia

PY - 2019/1/1

Y1 - 2019/1/1

N2 - The Tyrosine Kinase Receptor ErbB2 (HER2) when overexpressed in breast cancer (BC) is associated with poor prognosis. The monoclonal antibody Trastuzumab has become a standard treatment of ErbB2+BC. The antibody treatment has limited efficacy, often meets resistance and induces cardiotoxicity. T-cell recruiting bispecific antibody derivatives (TRBA) offer a more effective alternative to standard antibody therapy. We evaluated a panel of TRBAs targeting 3 different epitopes on the ErbB2 receptor either in a bivalent targeting tribody structure or as a monovalent scFv-fusion (BiTE format) for binding, cytotoxicity on Trastuzumab-resistant cell lines, and induction of cardiotoxicity. All three TRBAs bind with high affinity to the ErbB2 extracellular domain and a large panel of ErbB2-positive tumor cells. Tribodies had an increased in vitro cytotoxic potency as compared to BiTEs. It is interesting to note that, Tribodies targeting the epitopes on ErbB2 receptor domains I and II bind and activate lysis of mammary and gastric tumor cells more efficiently than a Tribody targeting the Trastuzumab epitope on domain IV. The first 2 are also active on Trastuzumab-resistant cancer cells lacking or masking the epitope recognized by Trastuzumab. None of the Tribodies studied showed significant toxicity on human cardiomyocytes. Altogether these results make these novel anti-ErbB2 bispecific Tribodies candidates for therapeutic development for treating ErbB2-positive Trastuzumab-resistant cancer patients.

AB - The Tyrosine Kinase Receptor ErbB2 (HER2) when overexpressed in breast cancer (BC) is associated with poor prognosis. The monoclonal antibody Trastuzumab has become a standard treatment of ErbB2+BC. The antibody treatment has limited efficacy, often meets resistance and induces cardiotoxicity. T-cell recruiting bispecific antibody derivatives (TRBA) offer a more effective alternative to standard antibody therapy. We evaluated a panel of TRBAs targeting 3 different epitopes on the ErbB2 receptor either in a bivalent targeting tribody structure or as a monovalent scFv-fusion (BiTE format) for binding, cytotoxicity on Trastuzumab-resistant cell lines, and induction of cardiotoxicity. All three TRBAs bind with high affinity to the ErbB2 extracellular domain and a large panel of ErbB2-positive tumor cells. Tribodies had an increased in vitro cytotoxic potency as compared to BiTEs. It is interesting to note that, Tribodies targeting the epitopes on ErbB2 receptor domains I and II bind and activate lysis of mammary and gastric tumor cells more efficiently than a Tribody targeting the Trastuzumab epitope on domain IV. The first 2 are also active on Trastuzumab-resistant cancer cells lacking or masking the epitope recognized by Trastuzumab. None of the Tribodies studied showed significant toxicity on human cardiomyocytes. Altogether these results make these novel anti-ErbB2 bispecific Tribodies candidates for therapeutic development for treating ErbB2-positive Trastuzumab-resistant cancer patients.

KW - ErbB2/HER2

KW - T-cell engager

KW - cancer

KW - immunotherapy

KW - tribody

UR - https://www.scopus.com/pages/publications/85058556465

U2 - 10.1097/CJI.0000000000000248

DO - 10.1097/CJI.0000000000000248

M3 - Article

SN - 1524-9557

VL - 42

SP - 1

EP - 10

JO - Journal of Immunotherapy

JF - Journal of Immunotherapy

IS - 1

ER -

T-cell Activating Tribodies as a Novel Approach for Efficient Killing of ErbB2-positive Cancer Cells

Abstract

OSS delle Nazioni Unite

Accesso al documento

Altri file e collegamenti

Fingerprint

Cita questo