Evidence map›Paper›PMID 41976311›Full record

ReviewCancers2026

Precision-Engineered CD3 T-Cell Engagers for Solid Tumours: Conditional Activation, Microenvironment Modulation, and Clinical Translation.

Md Zeyaullah, Abdullah M AlShahrani, Mohammad Suhail Khan, Md Faruque Ahmad, Abdelrhman A G Altijani, Awad Osman Abdalla Mohamed, Hytham Hummad, Ali Mohieldin, S Rehan Ahmad

Abstract readReview
In one paragraph

Review in Cancers, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

9 authors.

Md ZeyaullahDepartment of Basic Medical Science, College of Applied Medical Sciences, Khamis Mushayt Campus, King Khalid University (KKU), Abha 62561, Saudi Arabia.ORCID 0000-0003-0573-4129
Abdullah M AlShahraniDepartment of Basic Medical Science, College of Applied Medical Sciences, Khamis Mushayt Campus, King Khalid University (KKU), Abha 62561, Saudi Arabia.ORCID 0000-0002-9433-1913
Mohammad Suhail KhanDepartment of Public Health, College of Applied Medical Sciences, Khamis Mushayt Campus, King Khalid University (KKU), Abha 62561, Saudi Arabia.
Md Faruque AhmadDepartment of Clinical Nutrition, College of Nursing and Health Sciences, Jazan University, Jazan 45142, Saudi Arabia.ORCID 0000-0003-3353-0457
Abdelrhman A G AltijaniDepartment of Public Health, College of Applied Medical Sciences, Khamis Mushayt Campus, King Khalid University (KKU), Abha 62561, Saudi Arabia.ORCID 0000-0002-9560-2607
Awad Osman Abdalla MohamedDepartment of Anesthesia and Operations, College of Applied Medical Sciences, Khamis Mushait Campus, King Khalid University (KKU), Abha 62561, Saudi Arabia.ORCID 0009-0007-9286-877X
Hytham HummadDepartment of Anesthesia and Operations, College of Applied Medical Sciences, Khamis Mushait Campus, King Khalid University (KKU), Abha 62561, Saudi Arabia.
Ali MohieldinDepartment of Public Health, College of Applied Medical Sciences, Khamis Mushayt Campus, King Khalid University (KKU), Abha 62561, Saudi Arabia.ORCID 0000-0003-3038-3105
S Rehan AhmadHiralal Mazumdar Memorial College for Women, West Bengal State University, Kolkata 700035, West Bengal, India.ORCID 0000-0003-0796-5238

Funding

Deanship of Research and Graduate Studies at King Khalid University RGP2/361/46
6 · The paper itself

Abstract

backgroundT-cell-engaging bispecific antibodies (TCEs) have transformed haematological malignancy treatment (blinatumomab > 40% complete remission), yet solid tumour efficacy remains limited (<15% response rates) due to antigen heterogeneity, immunosuppressive microenvironments, and T-cell dysfunction. Systematic molecular engineering, biomarker-driven patient selection, and rational tumour microenvironment modulation are now collectively transforming TCEs from experimental agents into an adaptable platform therapy for solid tumours.

methodsReview of 55 phase I-III trials of CD3-based TCEs in solid tumours, including tarlatamab (DLL3-targeted, small-cell lung cancer) and xaluritamig (STEAP1-targeted, prostate cancer). Analysis of next-generation engineering strategies and resistance mechanisms via genomic and immunohistochemical data.

resultResponse rates now approach ~40% in selected settings, marking an inflection point. In extensive-stage small-cell lung cancer, tarlatamab achieved ~40% responses with definitive survival benefit (phase III HR 0.60, 95% CI 0.47-0.77; DISCUSSION: Three resistance mechanisms limit durability: (i) antigen heterogeneity (28-60% of progressors develop antigen-negative subclones); (ii) immunosuppressive microenvironments (stromal barriers, myeloid-derived suppressor cells, hypoxia); (iii) T-cell exhaustion (PD-1/TIM-3/LAG-3 co-expression).

conclusionsNext-generation TCE platforms integrating conditional activation, cytokine payloads, and checkpoint modulation-deployed with biomarker-guided selection and TME-modulating combinations-represent a transformative therapeutic strategy. With tarlatamab's phase III survival benefit establishing clinical proof-of-concept, and pivotal trials underway for xaluritamig and next-generation agents, TCEs are positioned to become standard-of-care platform therapies in biomarker-defined solid tumours by 2028-2030.

Indexed as

antigen heterogeneitybispecific antibodycancer immunotherapyCD3 T-cell engagercytokine-release syndromeDLL3small-cell lung cancertumour microenvironment

Identifiers

PMID41976311
PMCPMC13072142

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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.