Evidence map›Paper›PMID 41547950›Full record

ArticleNature communications2026

AI-guided CAR designs and targeted pathway modulation to enhance multi-antigen CAR T cell durability and overcome antigen escape.

Mohammad Sufyan Ansari, Varnit Chauhan, Aashi Singh, Areej Akhtar, Nisha Chaudhary, Reegina Tyagi, Divya, Kashif Husain, Sheetal Sharma, Ruquaiya Alam and 22 more

Abstract read
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing 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

9 citing papers in PubMed.

  1. Advancements in diagnosis and treatments of acute leukemia.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2026
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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

32 authors.

Mohammad Sufyan Ansari *Multidisciplinary Centre for Advanced Research and Studies, Jamia Millia Islamia, New Delhi, India.
Varnit Chauhan *Multidisciplinary Centre for Advanced Research and Studies, Jamia Millia Islamia, New Delhi, India.
Aashi SinghMultidisciplinary Centre for Advanced Research and Studies, Jamia Millia Islamia, New Delhi, India.
Areej AkhtarMultidisciplinary Centre for Advanced Research and Studies, Jamia Millia Islamia, New Delhi, India.
Nisha ChaudharyMultidisciplinary Centre for Advanced Research and Studies, Jamia Millia Islamia, New Delhi, India.
Reegina TyagiCellogen Therapeutics Pvt Ltd., Noida, Uttar Pradesh, India.
DivyaMultidisciplinary Centre for Advanced Research and Studies, Jamia Millia Islamia, New Delhi, India.
Kashif HusainMultidisciplinary Centre for Advanced Research and Studies, Jamia Millia Islamia, New Delhi, India.ORCID http://orcid.org/0009-0006-9624-027X
Sheetal SharmaMultidisciplinary Centre for Advanced Research and Studies, Jamia Millia Islamia, New Delhi, India.
Ruquaiya AlamMultidisciplinary Centre for Advanced Research and Studies, Jamia Millia Islamia, New Delhi, India.
Md ShakirMultidisciplinary Centre for Advanced Research and Studies, Jamia Millia Islamia, New Delhi, India.
Mehak PrachaMultidisciplinary Centre for Advanced Research and Studies, Jamia Millia Islamia, New Delhi, India.
Samreen AnjumMultidisciplinary Centre for Advanced Research and Studies, Jamia Millia Islamia, New Delhi, India.ORCID http://orcid.org/0009-0007-8473-0631
Mohd NadeemMultidisciplinary Centre for Advanced Research and Studies, Jamia Millia Islamia, New Delhi, India.
Prial TanejaMultidisciplinary Centre for Advanced Research and Studies, Jamia Millia Islamia, New Delhi, India.
Md Imam FaizanMultidisciplinary Centre for Advanced Research and Studies, Jamia Millia Islamia, New Delhi, India.
Iqbal AzmiMultidisciplinary Centre for Advanced Research and Studies, Jamia Millia Islamia, New Delhi, India.
Aditya Ramdas IyerCouncil of Scientific and Industrial Research (CSIR)-Institute of Genomics & Integrative Biology, New Delhi, India.
Pragya GuptaCouncil of Scientific and Industrial Research (CSIR)-Institute of Genomics & Integrative Biology, New Delhi, India.
Mehwish NafizCouncil of Scientific and Industrial Research (CSIR)-Institute of Genomics & Integrative Biology, New Delhi, India.
Shayan AliMultidisciplinary Centre for Advanced Research and Studies, Jamia Millia Islamia, New Delhi, India.
Insha Mohi UddinMultidisciplinary Centre for Advanced Research and Studies, Jamia Millia Islamia, New Delhi, India.
Momina JavidMultidisciplinary Centre for Advanced Research and Studies, Jamia Millia Islamia, New Delhi, India.
Zahoor Ahmad BhatMultidisciplinary Centre for Advanced Research and Studies, Jamia Millia Islamia, New Delhi, India.
Hamenth Kumar PalaniDepartment of Haematology, Christian Medical College, Ranipet Campus, Vellore, Tamil Nadu, India.
Amit Kumar SrivastavaCSIR-Indian Institute of Chemical Biology, Kolkata, West Bengal, India.
Ulaganathan MabalirajanCSIR-Indian Institute of Chemical Biology, Kolkata, West Bengal, India.
Vikram MathewsDepartment of Haematology, Christian Medical College, Ranipet Campus, Vellore, Tamil Nadu, India.ORCID http://orcid.org/0000-0001-9417-2353
Mohammad HusainDepartment of Biotechnology, Jamia Millia Islamia New Delhi, New Delhi, India.
Sivaprakash RamalingamCouncil of Scientific and Industrial Research (CSIR)-Institute of Genomics & Integrative Biology, New Delhi, India. sivaprakash@iitk.ac.in.
Gaurav KharyaCellogen Therapeutics Pvt Ltd., Noida, Uttar Pradesh, India. gaurav.kharya@gmail.com.ORCID http://orcid.org/0000-0003-2181-1825
Tanveer AhmadMultidisciplinary Centre for Advanced Research and Studies, Jamia Millia Islamia, New Delhi, India. tahmad7@jmi.ac.in.ORCID http://orcid.org/0009-0000-4562-566X

Funding

Indian Council of Medical Research (ICMR) ICMR-JRF-2020-HRD (31) (135027)
6 · The paper itself

Abstract

The persistence of CAR T cells and antigen escape remain major barriers to durable therapeutic success in hematologic malignancies. Our study integrates AI-guided design with targeted protein degradation to overcome these challenges. Utilizing an in-silico library of CAR constructs followed by an in vitro screening, we developed a predictive model, CARMSeD, which forecasts constructs prone to self-activation and dysfunction. Optimized bispecific CD20/CD19 CAR T cells demonstrate superior persistence and anti-tumor efficacy. To further improve durability, the platform incorporates a PROTAC-based module that selectively degrades AKT3, promoting FOXO4-driven mitochondrial fitness, central memory differentiation, and reduced mTOR signaling. We extended this strategy to develop a trispecific CAR T platform co-expressing a secretable CD3/CD22 bispecific engager, achieving potent tumor eradication even in CD19/CD20-negative malignancies demonstrates efficacy across patient-derived leukemia samples and solid tumor models. Together, our study introduces a next-generation AI-guided CAR T strategy that integrates structure-based optimization and intracellular modulation to improve persistence, broaden antigen coverage, and ensure durable therapeutic efficacy.

Indexed as

Immunotherapy, AdoptiveReceptors, Chimeric AntigenT-LymphocytesAnimalsAntigens, CD19Antigens, CD20CD3 ComplexCell Line, TumorHumansMiceProteolysis Targeting ChimeraProto-Oncogene Proteins c-aktReceptors, Antigen, T-CellSignal TransductionXenograft Model Antitumor AssaysAntigens, CD19Antigens, CD20CD3 ComplexProteolysis Targeting ChimeraProto-Oncogene Proteins c-aktReceptors, Antigen, T-CellReceptors, Chimeric Antigen

Identifiers

PMID41547950
PMCPMC12894905

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.