Evidence map›Paper›PMID 39606234›Full record

ReviewFrontiers in immunology2024

Logic-gated and contextual control of immunotherapy for solid tumors: contrasting multi-specific T cell engagers and CAR-T cell therapies.

Olivier Nolan-Stevaux, Richard Smith

Abstract readReview
In one paragraph

Review 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 38 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed, 1 pooled it
–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

38 citing papers in PubMed, 1 synthesis or guideline pooled it.

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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

2 authors.

Olivier Nolan-StevauxOncology Research, Gilead Sciences, Foster City, CA, United States.
Richard SmithCell Biology Research, Kite Pharma, Foster City, CA, United States.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

CAR-T cell and T cell engager therapies have demonstrated transformational efficacy against hematological malignancies, but achieving efficacy in solid tumors has been more challenging, in large part because of on-target/off-tumor toxicities and sub-optimal T cell anti-tumor cytotoxic functions. Here, we discuss engineering solutions that exploit biological properties of solid tumors to overcome these challenges. Using logic gates as a framework, we categorize the numerous approaches that leverage two inputs instead of one to achieve better cancer selectivity or efficacy in solid tumors with dual-input CAR-Ts or multi-specific TCEs. In addition to the "OR gate" and "AND gate" approaches that leverage dual tumor antigen targeting, we also review "contextual AND gate" technologies whereby continuous cancer-selective inputs such a pH, hypoxia, target density, tumor proteases, and immune-suppressive cytokine gradients can be creatively incorporated in therapy designs. We also introduce the notion of "output directionality" to distinguish dual-input strategies that mechanistically impact cancer cell killing or T cell fitness. Finally, we contrast the feasibility and potential benefits of the various approaches using CAR-T and TCE therapeutics and discuss why the promising "IF/THEN" and "NOT" gate types pertain more specifically to CAR-T therapies, but can also succeed by integrating both technologies.

Indexed as

Immunotherapy, AdoptiveNeoplasmsReceptors, Chimeric AntigenT-LymphocytesAnimalsAntigens, NeoplasmHumansTumor MicroenvironmentAntigens, NeoplasmReceptors, Chimeric AntigenAND gateCAR-Tlogic gatemultispecificNOT gateOR gateT cell bispecific antibodiesT cell engagers

Identifiers

PMID39606234
PMCPMC11599190

What Socratic 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 Socratic graph.