I
soPlexistechnologygivessscieenntitititstststsssttttheheheheaaaabbibibilitytoeeeexaxaamimimineneneaaaaandnd
characterizeimmunecell populatiooonsnn.IIInnnppparararrtittiticuccuular, IsoPllexexexis’’ssssinininglglglge-e-
cellfunctionalproteomicsallows researchersssto perform secretoryryrr
and intracellularr proteomic screening off heterogeneouscell populations
at single-cell resolution. Recently, IsooPlexis’ platform was instrummmental
inhelpingresearchers identifyyTTcell polyfunctionalityyasa keyyyfactorrin
positive responsesto checkpointinhibitor-adoptivecelltransferr (ACT)
combination therapyyagainst metastatic non-smallcelllungcancer
(NSCLC). Theirfindings, publishedinNature Medicine,^1 indicated
manageabletoxicity withtumor regressions—including complete
responses—inseveral patients.
Augmenting checkpoint inhibition with adoptive cell therapy
The discoveryy offimmune-checkpoint inhibitorsprovidedanimportant
breakthroughincancerr therapeutics. These drugs preventtumorr cells
from escapingTcell-mediated cytotoxicity;however, NSCLCtumors
areoften immunologically“cold,” meaningthat theycontain very
fewactivated,tumor-specificTcells. Toovercomethis challenge,
theteamadministeredcombination immunotherapy consistingof
the checkpointinhibitor nivolumab,followed by tumor-infiltrating
lymphocyte(TIL) infusion,in 16 metastatic NSCLC patients.
Elevenofthese 16 patientsshowedtumor regressionatthefirst
CTscan performedone monthfollowingTILadministration while
two patientsshowed complete responsesthat remained ongoing
- 5 years later.
Characterizing T cell functional behavior with single-cell
functional proteomics
The team employed IsoPlexis’ platform to examine T cell
polyfunctionality. Polyfunctionality isdefinedasthe ability off an
individualTTcelltosecrete multipledifferent cytokines afterr stimulation.
Measured usinga metriccalledthe polyfunctional strength index(PSI),
TTcell polyfunctionality hasbeen positively linked withcell therapy
potencyandvaccine efficacy. Inthis study,the researchersused
IsoPlexis’ technologyytoruna single-cellproteomepanel measuring
12 human cytokinesatonce. The IsoPlexis platformenabledtheteam
totest upto 1, 000 individualcellsacross 12 patients. Theyy foundCD4+
andCD 8 +TT cellPSItobe dramaticallyelevated immediatelyafter
TIL administration, witha significant proportion offTT cells capableof
secretingthreeorrmore cytokines.Moreover,whileCD4+TTcellPSI largely
returnedtobaseline levels byythefourth dayypost-TIL infusion,CD 8 +T
cell PSIcontinuedtobeelevated beyond dayy 12 afterrTILtreatment.
Improving therapeutics through improving understanding
IsoPlexis’ platformempowers researchersto discover the unique
multi-functionalcells via highly multiplexed single-cellfunctional
proteomics whichcorrelateto potency,persistence,andpatient
outcomein variousstudies.Here,it helpeda researchteambetter
define howTIL-based ACTT complementedor augmented nivolumab
checkpoint inhibitor therapy against NSCLC. Following ACT,
characterizingTT cell activityandbehaviorthat results inapositive
outcome willaidscientistsin identifying keydriver phenotypesthat
boostcell therapy efficacy.References- B.C. Creelan et al., “Tumor-infiltrating lymphocyte treatment for anti-PD-1-resistant
metastatic lung cancer: a phase 1 trial,” Nat Med, 27:1410-18, 2021.
IsoPlexis’ single-cell proteomics helps characterize T cell
properties for tumor-infiltrating lymphocyte (TIL) therapy against
non-small cell lung cancer
SPONSORED CONTENT
For Research Use Only. Not for Use in Diagnostic Procedures. isoplexis.c omIna NSCLC checkpoint inhibitor/TIL combination therapy study,
the polyfunctionality ofCD8+ T cells shows theimpact of TIL infusion
on patientimmune response.