Trial reportJournal of immunology (Baltimore, Md. : 1950)2012
Exhaustion of cytotoxic effector systems may limit monoclonal antibody-based immunotherapy in cancer patients.
Trial report in Journal of immunology (Baltimore, Md. : 1950), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
64 citing papers in PubMed, 1 synthesis or guideline pooled it, 115 citations in OpenAlex.
- Therapeutic Targeting of the Complement System: From Rare Diseases to Pandemics.Pharmacological reviews · 2021Pooled it
- Risk-adapted, ofatumumab-based chemoimmunotherapy and consolidation in treatment-naïve chronic lymphocytic leukemia: a phase 2 study.Leukemia & lymphoma · 2021Trial
- A phase II randomized trial comparing standard and low dose rituximab combined with alemtuzumab as initial treatment of progressive chronic lymphocytic leukemia in older patients: a trial of the ECOG-ACRIN cancer research group (E1908).American journal of hematology · 2016Trial
- Chemoimmunotherapy for relapsed/refractory and progressive 17p13-deleted chronic lymphocytic leukemia (CLL) combining pentostatin, alemtuzumab, and low-dose rituximab is effective and tolerable and limits loss of CD20 expression by circulating CLL cells.American journal of hematology · 2014Trial
- Induced resistance to ofatumumab-mediated cell clearance mechanisms, including complement-dependent cytotoxicity, in chronic lymphocytic leukemia.Journal of immunology (Baltimore, Md. : 1950) · 2014Trial
- Rapid clearance of rituximab may contribute to the continued high incidence of autoimmune hematologic complications of chemoimmunotherapy for chronic lymphocytic leukemia.Haematologica · 2013Trial
- Bispecific Antibody-Based Combination Therapies for B-Cell Lymphomas: Current Evidence and Future Perspectives.International journal of cancer · 2026Review
- Trogocytosis: Emerging insights into cellular communication, immunity, and pathogenesis.Molecular biology reports · 2026Review
- Efficacy of high-frequency low-dose rituximab and acalabrutinib in chronic lymphocytic leukemia.HemaSphere · 2026Article
- Article
- Article
- Antitumor Activities of a Humanized Cancer-Specific Anti-HER2 Monoclonal Antibody, humHInternational journal of molecular sciences · 2025Article
- Review
- Intercellular Transfer of Immune Regulatory Molecules Via Trogocytosis.Results and problems in cell differentiation · 2024Review
- Antibody-mediated phagocytosis in cancer immunotherapy.Immunological reviews · 2023Review
- Rituximab induced cytokine release with high serum IP-10 (CXCL10) concentrations is associated with infusion reactions.Leukemia research · 2023Article
- An anti-HER2 biparatopic antibody that induces unique HER2 clustering and complement-dependent cytotoxicity.Nature communications · 2023Article
- Revolutionizing cancer immunotherapy: unleashing the potential of bispecific antibodies for targeted treatment.Frontiers in immunology · 2023Review
- Avidity in antibody effector functions and biotherapeutic drug design.Nature reviews. Drug discovery · 2022Review
- FcγR-Mediated Trogocytosis 2.0: Revisiting History Gives Rise to a Unifying Hypothesis.Antibodies (Basel, Switzerland) · 2022Review
4 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
The CD20 mAb ofatumumab (OFA) induces complement-mediated lysis of B cells. In an investigator-initiated phase II trial of OFA plus chemotherapy for chronic lymphocytic leukemia (CLL), OFA treatment promoted partial CLL B cell depletion that coincided with reduced complement titers. Remaining CLL B cells circulated with bound OFA and covalently bound complement breakdown product C3d, indicative of ongoing complement activation. Presumably, neither complement- nor effector cell-based mechanisms were sufficiently robust to clear these remaining B cells. Instead, almost all of the bound OFA and CD20 was removed from the cells, in accordance with previous clinical studies that demonstrated comparable loss of CD20 from B cells after treatment of CLL patients with rituximab. In vitro experiments with OFA and rituximab addressing these observations suggest that host effector mechanisms that support mAb-mediated lysis and tumor cell clearance are finite, and they can be saturated or exhausted at high B cell burdens, particularly at high mAb concentrations. Interestingly, only a fraction of available complement was required to kill cells with CD20 mAbs, and killing could be tuned by titrating the mAb concentration. Consequently, maximal B cell killing of an initial and secondary B cell challenge was achieved with intermediate mAb concentrations, whereas high concentrations promoted lower overall killing. Therefore, mAb therapies that rely substantially on effector mechanisms subject to exhaustion, including complement, may benefit from lower, more frequent dosing schemes optimized to sustain and maximize killing by cytotoxic immune effector systems.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.