Evidence map›Paper›PMID 39605364›Full record

ArticlebioRxiv : the preprint server for biology2024

Unbiased discovery of antibody therapies that stimulate macrophage-mediated destruction of B-cell lymphoma.

Juliano Ribeiro, Carlota Pagès-Geli, Anna Meglan, Jose Velarde, Jasmine Blandin, Kyle Vaccaro, Thomas Wienclaw, Patricia Fernández-Guzmán, Cynthia K Hahn, Marta Crespo and 1 more

Abstract readPreprint
In one paragraph

Article in bioRxiv : the preprint server for biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Juliano RibeiroWhitehead Institute for Biomedical Research, Cambridge, MA 02142.
Carlota Pagès-GeliWhitehead Institute for Biomedical Research, Cambridge, MA 02142.
Anna MeglanWhitehead Institute for Biomedical Research, Cambridge, MA 02142.
Jose VelardeWhitehead Institute for Biomedical Research, Cambridge, MA 02142.
Jasmine BlandinWhitehead Institute for Biomedical Research, Cambridge, MA 02142.
Kyle VaccaroWhitehead Institute for Biomedical Research, Cambridge, MA 02142.
Thomas WienclawWhitehead Institute for Biomedical Research, Cambridge, MA 02142.
Patricia Fernández-GuzmánExperimental Hematology, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, C/ Natzaret, 115-117, 08035 Barcelona, Spain.
Cynthia K HahnDana-Farber Cancer Institute, Boston, MA 02115.
Marta CrespoExperimental Hematology, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, C/ Natzaret, 115-117, 08035 Barcelona, Spain.
Kipp WeiskopfWhitehead Institute for Biomedical Research, Cambridge, MA 02142.ORCID 0000-0002-9008-445X

Funding

KRAS inhibitors prime cancer cells for macrophage-mediated destructionR01CA279259 · NCI · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI KIPP A WEISKOPF · 2023 to 2026
$1.7M
NCI NIH HHS R01 CA279259
6 · The paper itself

Abstract

Macrophages are critical effectors of antibody therapies for lymphoma, but the best targets for this purpose remain unknown. Here, we sought to define a comprehensive repertoire of cell surface antigens that can be targeted to stimulate macrophage-mediated destruction of B-cell lymphoma. We developed a high-throughput assay to screen hundreds of antibodies for their ability to provoke macrophages to attack B-cell lymphoma cells. Across both mouse and human systems, we identified multiple unappreciated targets of opsonization as well as putative immune checkpoints. We used this information to engineer a compendium of 156 bispecific antibodies, and we identified dozens of bispecifics that dramatically stimulate macrophage-mediated cytotoxicity of lymphoma cells. Among these, a bispecific comprising a SIRPα decoy domain and a CD38-targeting arm (WTa2d1×CD38) exhibited maximal efficacy while minimizing the risk of hematologic toxicity. This bispecific stimulated robust anti-tumor responses in multiple xenograft models of aggressive B-cell lymphoma. Our approach can be directly applied to other cancers to rapidly discover bispecific antibodies that leverage anti-tumor responses by macrophages or other innate immune cells.

Identifiers

PMID39605364
PMCPMC11601295

What OpenQuestion holds

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Registered trials

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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.