Targeting CD19-positive lymphomas with the antibodydrug conjugate loncastuximab tesirine: preclinical evidence of activity as a single agent and in combination therapy Article Swipe
Chiara Tarantelli
,
David N. Wald
,
Nicolas Munz
,
Filippo Spriano
,
Alessio Bruscaggin
,
Eleonora Cannas
,
Luciano Cascione
,
Eugenio Gaudio
,
Alberto J. Arribas
,
Shivaprasad Manjappa
,
Gaetanina Golino
,
Lorenzo Scalise
,
Maria Teresa Cacciapuoti
,
Emanuele Zucca
,
Anastasios Stathis
,
Giorgio Inghirami
,
Patrick H. van Berkel
,
Davide Rossi
,
Paolo F. Caimi
,
Francesca Zammarchi
,
Francesco Bertoni
·
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.3324/haematol.2023.284197
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.3324/haematol.2023.284197
Antibody-drug conjugates (ADC) represent one of the most successful therapeutic approaches introduced into clinical practice in the last few years. Loncastuximab tesirine (ADCT-402) is a CD19-targeting ADC in which the antibody is conjugated through a protease cleavable dipeptide linker to a pyrrolobenzodiazepine dimer warhead (SG3199). Based on the results of a phase II study, loncastuximab tesirine was recently approved for adult patients with relapsed/refractory large B-cell lymphoma. We assessed the activity of loncastuximab tesirine using in vitro and in vivo models of lymphomas, correlated its activity with levels of CD19 expression, and identified combination partners providing synergy with the ADC. Loncastuximab tesirine was tested across 60 lymphoma cell lines. It had strong cytotoxic activity in B-cell lymphoma cell lines. The in vitro activity was correlated with the level of CD19 expression and intrinsic sensitivity of cell lines to the ADC’s warhead. Loncastuximab tesirine was more potent than other anti-CD19 ADC (coltuximab ravtansine, huB4-DGN462), although the pattern of activity across cell lines was correlated. The activity of loncastuximab tesirine was also largely correlated with cell line sensitivity to R-CHOP. Combinatorial in vitro and in vivo experiments identified the benefit of adding loncastuximab tesirine to other agents, especially BCL2 and PI3K inhibitors. Our data support the further development of loncastuximab tesirine for use as a single agent and in combination for patients affected by mature B-cell neoplasms. The results also highlight the importance of CD19 expression and the existence of lymphoma populations characterized by resistance to multiple therapies.
Related Topics
Concepts
Antibody-drug conjugate
CD19
In vivo
Cancer research
Lymphoma
Antibody
Cell culture
Medicine
In vitro
Pharmacology
Biology
Immunology
Monoclonal antibody
Biochemistry
Genetics
Biotechnology
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.3324/haematol.2023.284197
- https://haematologica.org/article/download/haematol.2023.284197/76976
- OA Status
- gold
- Cited By
- 12
- References
- 59
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4396762313
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W4396762313Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.3324/haematol.2023.284197Digital Object Identifier
- Title
-
Targeting CD19-positive lymphomas with the antibodydrug conjugate loncastuximab tesirine: preclinical evidence of activity as a single agent and in combination therapyWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2024Year of publication
- Publication date
-
2024-05-09Full publication date if available
- Authors
-
Chiara Tarantelli, David N. Wald, Nicolas Munz, Filippo Spriano, Alessio Bruscaggin, Eleonora Cannas, Luciano Cascione, Eugenio Gaudio, Alberto J. Arribas, Shivaprasad Manjappa, Gaetanina Golino, Lorenzo Scalise, Maria Teresa Cacciapuoti, Emanuele Zucca, Anastasios Stathis, Giorgio Inghirami, Patrick H. van Berkel, Davide Rossi, Paolo F. Caimi, Francesca Zammarchi, Francesco BertoniList of authors in order
- Landing page
-
https://doi.org/10.3324/haematol.2023.284197Publisher landing page
- PDF URL
-
https://haematologica.org/article/download/haematol.2023.284197/76976Direct link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://haematologica.org/article/download/haematol.2023.284197/76976Direct OA link when available
- Concepts
-
Antibody-drug conjugate, CD19, In vivo, Cancer research, Lymphoma, Antibody, Cell culture, Medicine, In vitro, Pharmacology, Biology, Immunology, Monoclonal antibody, Biochemistry, Genetics, BiotechnologyTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
12Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 9, 2024: 3Per-year citation counts (last 5 years)
- References (count)
-
59Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.populations | 239 |
| abstract_inverted_index.ravtansine, | 151 |
| abstract_inverted_index.sensitivity | 133, 175 |
| abstract_inverted_index.therapeutic | 9 |
| abstract_inverted_index.Antibody-drug | 0 |
| abstract_inverted_index.Combinatorial | 178 |
| abstract_inverted_index.Loncastuximab | 20, 100, 141 |
| abstract_inverted_index.characterized | 240 |
| abstract_inverted_index.huB4-DGN462), | 152 |
| abstract_inverted_index.loncastuximab | 54, 72, 166, 190, 207 |
| abstract_inverted_index.CD19-targeting | 25 |
| abstract_inverted_index.relapsed/refractory | 63 |
| abstract_inverted_index.pyrrolobenzodiazepine | 41 |
| cited_by_percentile_year.max | 99 |
| cited_by_percentile_year.min | 96 |
| countries_distinct_count | 2 |
| institutions_distinct_count | 21 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/3 |
| sustainable_development_goals[0].score | 0.7400000095367432 |
| sustainable_development_goals[0].display_name | Good health and well-being |
| citation_normalized_percentile.value | 0.95888676 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | True |