Evidence map›Paper›PMID 33408094›Full record

ArticleJournal for immunotherapy of cancer2021

Enhanced antitumor immunity by a novel small molecule HPK1 inhibitor.

Dan You, Stephen Hillerman, Gregory Locke, Charu Chaudhry, Caitlyn Stromko, Anwar Murtaza, Yi Fan, Jennifer Koenitzer, Yali Chen, Stephanie Briceno and 20 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal for immunotherapy of cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing 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

34 citing papers in PubMed.

  1. Review
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  8. Mechanisms of Anti-PD Therapy Resistance in Digestive System Neoplasms.Recent patents on anti-cancer drug discovery · 2025
    Review
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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

30 authors.

Dan YouOncology Discovery, Bristol-Myers Squibb Co, Princeton, New Jersey, USA.
Stephen HillermanOncology Discovery, Bristol-Myers Squibb Co, Princeton, New Jersey, USA.
Gregory LockeOncology Discovery, Bristol-Myers Squibb Co, Princeton, New Jersey, USA.
Charu ChaudhryOncology Discovery, Johnson and Johnson Limited, Spring House, Pennsylvania, USA.
Caitlyn StromkoOncology Discovery, Bristol-Myers Squibb Co, Princeton, New Jersey, USA.
Anwar MurtazaOncology Discovery, Bristol-Myers Squibb Co, Princeton, New Jersey, USA.
Yi FanOncology Discovery, Bristol-Myers Squibb Co, Princeton, New Jersey, USA.
Jennifer KoenitzerOncology Discovery, Bristol-Myers Squibb Co, Princeton, New Jersey, USA.
Yali ChenOncology Discovery, Bristol-Myers Squibb Co, Princeton, New Jersey, USA.
Stephanie BricenoOncology Discovery, Bristol-Myers Squibb Co, Princeton, New Jersey, USA.
Rajarshi BhadraOncology Discovery, Pfizer Inc, San Diego, California, USA.
Elizabeth DuperretOncology Discovery, Bristol-Myers Squibb Co, Princeton, New Jersey, USA.
Johnni Gullo-BrownOncology Discovery, Pfizer Inc, San Diego, California, USA.
Chan GaoOncology Discovery, Bristol-Myers Squibb Co, Princeton, New Jersey, USA.
Dandan ZhaoOncology Discovery, Bristol-Myers Squibb Co, Princeton, New Jersey, USA.
John FederOncology Discovery, Bristol-Myers Squibb Co, Princeton, New Jersey, USA.
Joshua CurtinOncology Discovery, Johnson and Johnson Limited, Spring House, Pennsylvania, USA.
Andrew P DegnanOncology Discovery, Bristol-Myers Squibb Co, Princeton, New Jersey, USA.
Godwin KumiOncology Discovery, Bristol-Myers Squibb Co, Princeton, New Jersey, USA.
Mark WittmanOncology Discovery, Bristol-Myers Squibb Co, Cambridge, Massachusetts, USA.
Benjamin M JohnsonOncology Discovery, Bristol-Myers Squibb Co, Cambridge, Massachusetts, USA.
Karen E ParrishOncology Discovery, Bristol-Myers Squibb Co, Princeton, New Jersey, USA.
Giridharan GokulranganOncology Discovery, Bristol-Myers Squibb Co, Princeton, New Jersey, USA.
John MorrisonOncology Discovery, Bristol-Myers Squibb Co, Princeton, New Jersey, USA.
Michael QuigleyOncology Discovery, Gilead Sciences Inc, Foster City, California, USA.
John T HuntOncology Discovery, Bristol-Myers Squibb Co, Princeton, New Jersey, USA.
Luisa Salter-CidOncology Discovery, Gossamer Bio, San Diego, California, USA.
Emma LeesOncology Discovery, Bristol-Myers Squibb Co, Cambridge, Massachusetts, USA.
Miguel A SanjuanOncology Discovery, Bristol-Myers Squibb Co, Princeton, New Jersey, USA.
Jinqi LiuOncology Discovery, Bristol-Myers Squibb Co, Princeton, New Jersey, USA jinqi.liu@bms.com.ORCID 0000-0002-0094-9801

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundHematopoietic progenitor kinase 1 (HPK1 or MAP4K1) has been demonstrated as a negative intracellular immune checkpoint in mediating antitumor immunity in studies with HPK1 knockout and kinase dead mice. Pharmacological inhibition of HPK1 is desirable to investigate the role of HPK1 in human immune cells with therapeutic implications. However, a significant challenge remains to identify a small molecule inhibitor of HPK1 with sufficient potency, selectivity, and other drug-like properties suitable for proof-of-concept studies. In this report, we identified a novel, potent, and selective HPK1 small molecule kinase inhibitor, compound K (CompK). A series of studies were conducted to investigate the mechanism of action of CompK, aiming to understand its potential application in cancer immunotherapy.

methodsHuman primary T cells and dendritic cells (DCs) were investigated with CompK treatment under conditions relevant to tumor microenvironment (TME). Syngeneic tumor models were used to assess the in vivo pharmacology of CompK followed by human tumor interrogation ex vivo.

resultsCompK treatment demonstrated markedly enhanced human T-cell immune responses under immunosuppressive conditions relevant to the TME and an increased avidity of the T-cell receptor (TCR) to recognize viral and tumor-associated antigens (TAAs) in significant synergy with anti-PD1. Animal model studies, including 1956 sarcoma and MC38 syngeneic models, revealed improved immune responses and superb antitumor efficacy in combination of CompK with anti-PD-1. An elevated immune response induced by CompK was observed with fresh tumor samples from multiple patients with colorectal carcinoma, suggesting a mechanistic translation from mouse model to human disease.

conclusionCompK treatment significantly improved human T-cell functions, with enhanced TCR avidity to recognize TAAs and tumor cytolytic activity by CD8+ T cells. Additional benefits include DC maturation and priming facilitation in tumor draining lymph node. CompK represents a novel pharmacological agent to address cancer treatment resistance.

Indexed as

AnimalsAntineoplastic AgentsBone NeoplasmsCell LineCell ProliferationCell SurvivalGene Expression Regulation, NeoplasticGinsenosidesHumansMiceProtein Serine-Threonine KinasesReceptors, Antigen, T-CellSarcomaTreatment OutcomeTumor MicroenvironmentXenograft Model Antitumor AssaysAntineoplastic Agentsginsenoside compound KGinsenosideshematopoietic progenitor kinase 1Protein Serine-Threonine KinasesReceptors, Antigen, T-Celladaptive ImmunityCD8-positive T-Lymphocytesdendritic cellslymphocytestumor-Infiltratingtumor microenvironment

Identifiers

PMID33408094
PMCPMC7789447

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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.