Evidence map›Paper›PMID 38786100›Full record

ArticleCells2024

Pre-Clinical Assessment of SAR442257, a CD38/CD3xCD28 Trispecific T Cell Engager in Treatment of Relapsed/Refractory Multiple Myeloma.

Anna Luise Grab, Peter S Kim, Lukas John, Kamlesh Bisht, Hongfang Wang, Anja Baumann, Helgi Van de Velde, Irene Sarkar, Debarati Shome, Philipp Reichert and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cells, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing 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

13 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Review
  6. Review
  7. Review
  8. Review
  9. Review
  10. Article
  11. Review
  12. Review
  13. Review
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

15 authors.

Anna Luise GrabHeidelberg Myeloma Center, Department of Medicine V, Medical Faculty Heidelberg and University Hospital, Heidelberg University, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany.
Peter S KimSanofi Research and Development, Sanofi North America, Cambridge, MA 02141, USA.
Lukas JohnHeidelberg Myeloma Center, Department of Medicine V, Medical Faculty Heidelberg and University Hospital, Heidelberg University, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany.ORCID 0000-0001-8178-6890
Kamlesh BishtSanofi Research and Development, Sanofi North America, Cambridge, MA 02141, USA.
Hongfang WangSanofi Research and Development, Sanofi North America, Cambridge, MA 02141, USA.
Anja BaumannHeidelberg Myeloma Center, Department of Medicine V, Medical Faculty Heidelberg and University Hospital, Heidelberg University, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany.
Helgi Van de VeldeSanofi Research and Development, Sanofi North America, Cambridge, MA 02141, USA.
Irene SarkarLUMICKS, 1059 CM Amsterdam, The Netherlands.ORCID 0009-0006-7349-9502
Debarati ShomeLUMICKS, 1059 CM Amsterdam, The Netherlands.
Philipp ReichertGMMG Central Study Lab, Biobank, University Hospital Heidelberg, 69120 Heidelberg, Germany.ORCID 0000-0001-7583-6222
Calin MantaHeidelberg Myeloma Center, Department of Medicine V, Medical Faculty Heidelberg and University Hospital, Heidelberg University, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany.
Stefanie GryzikHeidelberg Myeloma Center, Department of Medicine V, Medical Faculty Heidelberg and University Hospital, Heidelberg University, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany.
Rogier M ReijmersLUMICKS, 1059 CM Amsterdam, The Netherlands.
Niels WeinholdHeidelberg Myeloma Center, Department of Medicine V, Medical Faculty Heidelberg and University Hospital, Heidelberg University, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany.
Marc S RaabHeidelberg Myeloma Center, Department of Medicine V, Medical Faculty Heidelberg and University Hospital, Heidelberg University, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany.

Funding

Flagship initiative for engineering molecular systems, University Heidelberg, Germany ExU 6.1.25
6 · The paper itself

Abstract

Current treatment strategies for multiple myeloma (MM) are highly effective, but most patients develop relapsed/refractory disease (RRMM). The anti-CD38/CD3xCD28 trispecific antibody SAR442257 targets CD38 and CD28 on MM cells and co-stimulates CD3 and CD28 on T cells (TCs). We evaluated different key aspects such as MM cells and T cells avidity interaction, tumor killing, and biomarkers for drug potency in three distinct cohorts of RRMM patients. We found that a significantly higher proportion of RRMM patients (86%) exhibited aberrant co-expression of CD28 compared to newly diagnosed MM (NDMM) patients (19%). Furthermore, SAR442257 mediated significantly higher TC activation, resulting in enhanced MM killing compared to bispecific functional knockout controls for all relapse cohorts (Pearson's r = 0.7). Finally, patients refractory to anti-CD38 therapy had higher levels of TGF-β (up to 20-fold) compared to other cohorts. This can limit the activity of SAR442257. Vactoserib, a TGF-β inhibitor, was able to mitigate this effect and restore sensitivity to SAR442257 in these experiments. In conclusion, SAR442257 has high potential for enhancing TC cytotoxicity by co-targeting CD38 and CD28 on MM and CD3/CD28 on T cells.

Indexed as

ADP-ribosyl Cyclase 1Antibodies, BispecificMultiple MyelomaT-LymphocytesCD28 AntigensCD3 ComplexCell Line, TumorHumansMembrane GlycoproteinsRecurrenceADP-ribosyl Cyclase 1Antibodies, BispecificCD28 AntigensCD38 protein, humanCD3 ComplexMembrane Glycoproteinscell aviditymicroenvironmentrefractory multiple myelomaT cell engager

Identifiers

PMID38786100
PMCPMC11120574

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 Socratic graph.