ArticleJournal for immunotherapy of cancer2025
Fc-competent TIGITx4-1BB bispecific antibody exerts potent long-lasting antitumor activity by potentiating CD8
Article in Journal for immunotherapy of cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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.
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.
Who cites it
4 citing papers in PubMed.
- Post-translational modifications of immune checkpoints: molecular mechanisms, tumor microenvironment remodeling, and therapeutic implications.Journal of biomedical science · 2026Review
- Advancing immunotherapy via multiple immune cells co-engagement.Frontiers in immunology · 2026Review
- Overcoming resistance to anti-PD-1/PD-L1 therapy in cancer.Cancer drug resistance (Alhambra, Calif.) · 2026Review
- The role of immune checkpoint molecules in cancers.Frontiers in immunology · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTIGIT was identified as a target immune checkpoint for overcoming resistance to PD-(L)1-blocking antibodies. However, the clinical efficacies of TIGIT antibodies were moderate in monotherapy and mixed in combination with PD-(L)1 antibodies. 4-1BB, a strong inducible costimulatory receptor, is another attractive target in antitumor therapeutics. This study investigated whether ABL112, an Fc-competent bispecific antibody targeting TIGIT and 4-1BB (TIGITx4-1BB), would enhance antitumor activity via Fcγ receptor (FcγR)-mediated macrophage activation and antibody-dependent cell-mediated functions.
methodsTIGIT-dependent 4-1BB activation and TIGIT-blocking activity were assessed using reporter Jurkat T cell lines expressing 4-1BB and TIGIT, respectively. In vivo antitumor activity was confirmed in h4-1BB knock-in mice. The main immune cell subsets associated with the antitumor activity of ABL112 were identified using antibodies for depleting specific immune cell subtypes or FcγR-blocking antibodies. The effects of a combined pembrolizumab or atezolizumab treatment with ABL112 were assessed in two mouse models with different genetic backgrounds. Statistical analysis was performed using one-way or two-way analysis of variance (ANOVA) with Dunnett's multiple-comparison test or one-way ANOVA with Fisher's multiple-comparison test.
resultsABL112 restored T cell activity by blocking TIGIT-CD155 interactions, based on a TIGIT blockade reporter assay. ABL112, an Fc-competent TIGITx4-1BB bispecific antibody, showed strong FcγRI-dependent 4-1BB activation along with TIGIT-dependent 4-1BB activation. In H22 tumor models expressing high levels of endogenous CD155, both ABL112 and parent TIGIT single-domain Ab showed potent tumor-suppressive activity; however, only ABL112 exerted long-lasting antitumor activity. ABL112 induced a marked decrease in Treg numbers, while augmenting the absolute number of CD8
conclusionsThrough multiple mechanisms of action, ABL112 exerted potent tumor-killing activity and immune memory response alone or in combination with anti-PD-(L)1 therapies, representing a promising new cancer treatment strategy.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.