Evidence map›Paper›PMID 39776903›Full record

ArticleFrontiers in immunology2024

Soluble factors released by peripheral blood-derived CAR-NK cells cause bystander myeloid cell activation.

Supreet Khanal, Alan Baer, Md Kamal Hossain, Winston Colon-Moran, Santosh Panthi, Nirjal Bhattarai

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Frontiers in immunology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
  4. Frontiers in immunology · 2026
    Review
  5. Article
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

6 authors.

Supreet KhanalTumor Vaccine and Biotechnology Branch, Office of Cellular Therapy and Human Tissues, Office of Therapeutic Products, Center for Biologics Evaluation and Research, United States Food and Drug Administration (U.S. FDA), Silver Spring, MD, United States.
Alan BaerTumor Vaccine and Biotechnology Branch, Office of Cellular Therapy and Human Tissues, Office of Therapeutic Products, Center for Biologics Evaluation and Research, United States Food and Drug Administration (U.S. FDA), Silver Spring, MD, United States.
Md Kamal HossainTumor Vaccine and Biotechnology Branch, Office of Cellular Therapy and Human Tissues, Office of Therapeutic Products, Center for Biologics Evaluation and Research, United States Food and Drug Administration (U.S. FDA), Silver Spring, MD, United States.
Winston Colon-MoranTumor Vaccine and Biotechnology Branch, Office of Cellular Therapy and Human Tissues, Office of Therapeutic Products, Center for Biologics Evaluation and Research, United States Food and Drug Administration (U.S. FDA), Silver Spring, MD, United States.
Santosh PanthiTumor Vaccine and Biotechnology Branch, Office of Cellular Therapy and Human Tissues, Office of Therapeutic Products, Center for Biologics Evaluation and Research, United States Food and Drug Administration (U.S. FDA), Silver Spring, MD, United States.
Nirjal BhattaraiTumor Vaccine and Biotechnology Branch, Office of Cellular Therapy and Human Tissues, Office of Therapeutic Products, Center for Biologics Evaluation and Research, United States Food and Drug Administration (U.S. FDA), Silver Spring, MD, United States.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Introduction: CAR-T cell therapy is associated with life-threatening inflammatory toxicities, partly due to the activation and secretion of inflammatory cytokines by bystander myeloid cells (BMCs). However, due to limited clinical data, it is unclear whether CAR-NK cells cause similar toxicities. Methods: We characterized the soluble factors (SFs) released by activated human CAR-T and CAR-NK cells and assessed their role in BMC activation (BMCA). Results: We found that SFs from both activated, peripheral blood-derived CAR-T (PB-CAR-T) and CAR-NK (PB-CAR-NK) cells induced BMCA; however, PB-CAR-NK cells caused significantly lower BMCA compared to PB-CAR-T cells. Interestingly, SFs from cord-blood-derived (CB) NK cells caused little to no BMCA, consistent with previous clinical studies showing minimal inflammatory toxicity with CB-CAR-NK cells. Comparative analysis of SFs released by PB-NK and PB-CAR-NK cells following CAR-dependent and CAR-independent activation revealed several candidate factors with the potential to cause BMCA. Antibody-mediated neutralization studies identified a combination of four factors that contribute to PB-CAR-NK cell-mediated BMCA. siRNA-mediated knockdown studies confirmed that inactivating these four factors in PB-CAR-NK cells significantly reduces BMCA. Importantly, neutralization or knockdown of these four factors did not affect CAR-NK cell potency. Discussion: These data suggest that specific SFs released by PB-CAR-NK cells activate BMCs and have the potential to contribute to inflammatory toxicities. Furthermore, inactivation of these four factors in PB-CAR-NK cells could reduce inflammatory toxicities and improve safety of PB-CAR-NK cell therapy without compromising potency.

Indexed as

Bystander EffectImmunotherapy, AdoptiveKiller Cells, NaturalMyeloid CellsReceptors, Chimeric AntigenCytokinesHumansLymphocyte ActivationCytokinesReceptors, Chimeric AntigenCAR (chimeric antigen receptor)CRSinflammationneurotoxicityNK cell

Identifiers

PMID39776903
PMCPMC11703831

What OpenQuestion 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 OpenQuestion graph.