Evidence map›Paper›PMID 41007874›Full record

ReviewBiomedicines2025

Allogeneic NKG2D CAR-T Cell Therapy: A Promising Approach for Treating Solid Tumors.

Sabir A Mukhametshin, Elvina M Gilyazova, Damir R Davletshin, Irina A Ganeeva, Ekaterina A Zmievskaya, Vitaly V Chasov, Alexsei V Petukhov, Aigul Kh Valiullina, Sheila Spada, Emil R Bulatov

Abstract readReview
In one paragraph

Review in Biomedicines, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
  4. 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

10 authors.

Sabir A MukhametshinInstitute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia.
Elvina M GilyazovaInstitute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia.
Damir R DavletshinInstitute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia.
Irina A GaneevaInstitute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia.
Ekaterina A ZmievskayaInstitute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia.
Vitaly V ChasovInstitute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia.
Alexsei V PetukhovLaboratory of Molecular Oncology, National Laboratory Astana, Astana 010000, Kazakhstan.
Aigul Kh ValiullinaInstitute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia.
Sheila SpadaTumor Immunology and Immunotherapy Unit, IRCCS-Regina Elena National Cancer Institute, 00144 Rome, Italy.
Emil R BulatovInstitute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia.ORCID 0000-0003-2961-0032

Funding

Russian Science Foundation #24-74-00092
6 · The paper itself

Abstract

Chimeric Antigen Receptor (CAR)-T cell therapy has transformed the treatment landscape of cancer, yet major challenges remain in enhancing efficacy, reducing adverse effects, and expanding accessibility. Autologous CAR-T cells, derived from individual patients, have achieved remarkable clinical success in hematologic malignancies; however, their highly personalized nature limits scalability, increases costs, and delays timely treatment. Allogeneic CAR-T cells generated from healthy donors provide an "off-the-shelf" alternative but face two critical immune barriers: graft-versus-host disease (GvHD), caused by donor T-cell receptor (TCR) recognition of host tissues, and host-versus-graft rejection, mediated by recipient immune responses against donor HLA molecules. Recent advances in genome engineering, particularly Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9, allow precise modification of donor T cells to overcome these limitations. For example, TRAC gene knockout eliminates TCR expression, preventing GvHD, while disruption of HLA molecules reduces immunogenicity without impairing cytotoxicity. Beyond hematologic cancers, CRISPR-edited allogeneic CAR-T cells targeting the NKG2D receptor have shown promise in preclinical studies and early-phase trials. NKG2D CAR-T cells recognize stress ligands (MICA/B, ULBP1-6) expressed on over 80% of diverse solid tumors, including pancreatic and ovarian cancers, thereby broadening therapeutic applicability. Nevertheless, the genomic editing process carries risks of off-target effects, including potential disruption of tumor suppressor genes and oncogenes, underscoring the need for stringent safety and quality control. This review examines the distinguishing features of allogeneic versus autologous CAR-T therapy, with a particular focus on NKG2D-based allogeneic CAR-T approaches for solid tumors. We summarize current strategies to mitigate immune barriers, discuss practical manufacturing challenges, and analyze available clinical data on NKG2D CAR-T trials. Collectively, these insights underscore both the promise and the hurdles of developing safe, universal, and scalable allogeneic CAR-T therapies for solid malignancies.

Indexed as

adoptive cell therapyallogeneic CAR-T therapycancerCRISPR/Cas9NKG2D receptor

Identifiers

PMID41007874
PMCPMC12467792

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.