Tumor Regression in Cancer Patients by Very Low Doses of a T Cell–Engaging Antibody
Abstract
Previous attempts have shown the potential of T cells in immunotherapy of cancer. Here, we report on the clinical activity of a bispecific antibody construct called blinatumomab, which has the potential to engage all cytotoxic T cells in patients for lysis of cancer cells. Doses as low as 0.005 milligrams per square meter per day in non–Hodgkin's lymphoma patients led to an elimination of target cells in blood. Partial and complete tumor regressions were first observed at a dose level of 0.015 milligrams, and all seven patients treated at a dose level of 0.06 milligrams experienced a tumor regression. Blinatumomab also led to clearance of tumor cells from bone marrow and liver. T cell–engaging antibodies appear to have therapeutic potential for the treatment of malignant diseases.
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The first approved bsAbs are catumaxomab and blinatumomab.
“This is best exemplified by the first approved bsAbs, catumaxomab (a bsAb binds both CD3 on cytotoxic T cells and EpCAM on human adenocarcinomas,88) and blinatumomab (a CD19 × CD3 targeting bispecific scFv antibody fragment.89)”
From Tutorial on monoclonal antibody pharmacokinetics and its considerations in early development (2018) · cites this paper as [89]
All seven patients treated at a dose level of 60 μg experienced tumor regression.
“All seven patients treated at a dose level of 60 μg experienced a tumor regression. 54”
From Bispecific antibodies for cancer therapy: The light at the end of the tunnel? (2009) · cites this paper as [54]
In 2008, the first result of a Phase 1 clinical study indicated that doses as low as 5 μg per square meter per day in relapsed NHL patients led to elimination of target cells in blood.
“In 2008, the first result of a Phase 1 clinical study indicated that doses as low as 5 μg per square meter per day in relapsed NHL patients led to an elimination of target cells in blood.”
From Bispecific antibodies for cancer therapy: The light at the end of the tunnel? (2009) · cites this paper as [54]
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- Authors
- Bargou, R., Leo, E., Zugmaier, G., Klinger, M., Goebeler, M., Knop, S., Noppeney, R., Viardot, A., Hess, G., Schuler, M., Einsele, H., Brandl, C., Wolf, A., Kirchinger, P., Klappers, P., Schmidt, M., Riethmüller, G., Reinhardt, C., Baeuerle, P. A., & Kufer, P.
- Affiliations
- University of Würzburg (DE)
- Interdisciplinary Phase I/II Unit of the University of Würzburg, Klinikstraße 6-8, 97070 Würzburg, Germany.
- Corresponding author
- Bargou, Ralf
- Leo, Eugen
- Baeuerle, Patrick A.
- ORCID
- Venue
- Science
- Published
- 2008-08-15
- Volume
- 321
- Issue
- 5891
- Pages
- 974-977
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W1991644988
- Cited by
- 1,078
- References
- 28
- Citations by year
- 2026: 36 · 2025: 52 · 2024: 40 · 2023: 52 · 2022: 37 · 2021: 63 · 2020: 55 · 2019: 58 · 2018: 53 · 2017: 64 · 2016: 75 · 2015: 80 · 2014: 77 · 2013: 78 · 2012: 75
- FWCI
- 46.59
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Health Sciences › Medicine › Oncology › CAR-T cell therapy research
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- blinatumomab, bispecific antibodies, T cell-engaging antibody, tumor regression, non-Hodgkin lymphoma, adoptive T cell therapy, cytotoxic T lymphocytes
- MeSH terms
- Antineoplastic Agents, B-Lymphocytes, Humans, Immunologic Memory, Lymphoma, Follicular, Recurrence, T-Lymphocytes, T-Lymphocytes, Cytotoxic, Leukemia, Lymphocytic, Chronic, B-Cell, Immunophenotyping, Lymphoma, B-Cell, Antibodies, Bispecific, Lymphocyte Count, Lymphoma, Mantle-Cell
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