Several high profile publications and presentations demonstrate the value of our MAP (Multi-Analyte Profile) and Simoa platforms for measuring panels of immune- and cancer-related soluble factors present in peripheral blood from patients enrolled in immune therapies.
IFN-gamma chemokines CXCL9, CXCL10, IL-2RA were increased with budigalimab treatment, consistent with other PD-1 inhibitors. 1
- Model informed dosing regimen and phase I results of the anti-PD-1 antibody budigalimab (ABBV-181). (2020) Powderly J, et al. Clin Trans Sci. 2020 Aug 8. doi: 10.1111/cts.12855.
Serum immune markers at baseline and on-therapy are associated with survival and tumor regression with checkpoint inhibition therapies.2
- Serum interleukin-6 and C-reactive protein are associated with survival in melanoma patients receiving immune checkpoint inhibition. (2020) Laino AS, et al. J Immunother Cancer. 2020;8:e000842. doi:10.1136/jitc-2020-000842
Baseline serum biomarker signatures prognostic for nivolumab drug clearance & overall survival in melanoma and renal cancer. 3,4
- Development of a prognostic composite cytokine signature based on the correlation with nivolumab clearance: translational PK/PD analysis in patients with renal cell carcinoma. (2019) Wang R, et al. J Immunother Cancer. 2019 Dec 11;7(1):348.
- A machine-learning approach to Identify a prognostic cytokine signature that is associated with nivolumab clearance in patients with advanced melanoma. (2019) Wang R, et al. Clin Pharmacol Ther. 2020 Apr;107(4):978-987. doi: 10.1002/cpt.1724.
Circulating immune and T-cell activation biomarker levels elevated in CX-072 treatment are consistent with PD-1/PD-L1 pathway activation.5
- Evidence of intratumoral localization, activation, and immunomodulatory effect of CX-072, a PROBODY therapeutic targeting PD-L1, in a phase ½ trial. (2020) Lyman SK, et al. P310 ASCO20 Virtual Scientific Program May 29-31.
Elevated baseline levels of circulating inflammatory, myeloid (CRP, IL-6, S100A12) and angiogenic proteins (ANGPT2, vWF, ICAM1) correlated with shorter OS.6
- Correlation of angiogenic and immunomodulatory proteins with clinical outcomes of durvalumab (anti-PD-L1) in recurrent/metastatic head and neck squamous cell carcinoma. (2019) Guo X, et al. P6048 ASCO. June 1-4. Chicago, IL.
High circulating levels of IL-6 is correlated with poor prognosis of HCC patients and positively correlated with tumor PD-L1 expression.7
- IL-6/JAK1 pathway drives PD-L1 Y112 phosphorylation to promote cancer immune evasion. (2019) Chan LC, et al. J Clin Invest. 2019 Jul 15;129(8):3324-3338.
TGFb inhibition: immune-related biomarkers with pharmacodynamic, prognostic and predictive potential.8,9,10,11
- TGFb receptor inhibitor galunisertib is linked to inflammation- and remodeling-related proteins in patients with pancreatic cancer. (2019) Melisi D, et al. Cancer Chemother Pharmacol. 2019 May; 83(5):975-991.
- Phase 1b/2a study of galunisertib, a small molecule inhibitor of transforming growth factor-beta receptor I, in combination with standard temozolomide-based radiochemotherapy in patients with newly diagnosed malignant glioma. (2020) Wick A, et al. Invest New Drugs. 2020 Oct;38(5):1570-1579. doi: 10.1007/s10637-020-00910-9.
- Biomarkers and overall survival in patients with advanced hepatocellular carcinoma treated with TGF-beta R1 inhibitor galunisertib. (2020) Giannelli G, et al. PLoS ONE. 2020 Mar 25;15(3):e0222259. doi: 10.1371/journal.pone.0222259.
- AVID200, first-in-class TGF-beta 1 and 3 selective and potent inhibitor: safety and biomarker results of a phase I monotherapy dose-escalation study in patients with advanced solid tumors. (2020) Yap TA, et al. P3587. ASCO Virtual Scientific Program. 2020. https://meetinglibrary.asco.org/record/187808/abstract
TruCulture cytokine analysis of adenosine A2A receptor engagement and dose dependent pharmacodynamic release of immune suppression.12
- EOS100850 inhibits A2A receptor signaling in human whole blood: two pharmacodynamic assays to monitor EOS100850 activity in clinical studies. (2019) Martinoli C, et al. P4154. AACR Mar 29- Apr 3. Atlanta, GA.
Elevated levels of serum inflammatory proteins including APO E pre-vaccination are associated with the clinical non-responder phenotype and shorter PFS.13
- Serum apolipoprotein E and other inflammatory markers can identify non-responding patients to a dendritic cell vaccine. (2019) Leeman H, et al. Transl Oncol. 2019 Mar;12(3):397-403.
Activation of the immune system in a complete responder as reflected by levels of peripheral interferon-γ-related cytokines (IL-18, CXCL10), increased proliferating NK and CD8+ T cells, and tumor immune microenvironment signatures.14
- Tumor immune microenvironment and genomic evolution in a patient with metastatic triple negative breast cancer and a complete response to atezolizumab. (2019) Molinero L, et al. J Immunuther Cancer. 2019 Oct 23;7(1):274.
A single nivolumab dose does not cause unexpected safety findings or ‘cytokine storm’ in sepsis patients with organ dysfunction and low lymphocyte counts.15
- Immune checkpoint inhibition in sepsis: a phase 1b randomized study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of nivolumab. (2019) Hotchkiss RS, et al. Intensive Care Med. 2019 Oct;45(10) 1360-1371.
Circulating levels of IFNγ as measured by an ultrasensitive immunoassay are pharmacodynamic for an immune stimulating agent and prognostic for OS.16
- The immunomodulatory effects of cancer therapy on IFN-gamma responses in the periphery. (2018) Brunet LA, et al. P81 SITC. Nov 9-11. National Harbor, MD.
Circulating protein biomarkers including soluble Axl are pharmacodynamic & potentially predicative of patient response.17,18,19,20
- Durable responses observed in elderly AML patients unfit for intensive chemotherapy with first-in-class selective AXL inhibitor bemcentinib (BGB324) in combination with LDAC: phase II open-label study. (2019) Loges S, et al. P3943. ASH Dec 9. Orlando, FL.
- Phase II open-label, multi-centre study of bemcentinib (BGB324), a first-in-class selective AXL inhibitor, in combination with pembrolizumab in patients with advanced NSCLC. (2018) Lorens J, et al. P3078. ASCO June 1-4. Chicago, IL.
- Analysis of anti-leukaemic activity, predictive biomarker candidates, immune activation and pharmacodynamics in R/R AML and MDS in response to treatment with bemcentinib (BGB324), a first-in-class selective AXL inhibitor, in a phase II open label, multi-centre study. (2018) Gjertsen BT, et al. P7020. ASCO June 1-4. Chicago, IL.
- A randomized phase Ib/II study of the selective small molecule AXL inhibitor bemcentinib (BGB324) in combination with either dabrafenib/trametinib or pembrolizumab in patients with metastatic melanoma. (2018) Oddbjorn S, et al. P3078. ASCO June 1-4. Chicago, IL.
A large cross-sectional retrospective study of over 2,000 patients demonstrating that serum IL-8 is a promising clinical biomarker for patients that benefit from I-O therapy.21,22
- Elevated serum interleukin-8 is associated with enhanced intratumor neutrophils and reduced clinical benefit of immune-checkpoint inhibitors. (2020) Schalper KA, et al. Nat Med. 2020 May;26(5):688-692. doi: 10.1038/s41591-020-0856-x.
- Serum interleukin 8 (IL-8) may serve as a biomarker of response to immuno-oncology (I-O) therapy. (2018) Carleton M, et al. P3025. ASCO June 1-4. Chicago, IL.
If high levels of IL-8 reduces the effectiveness of anti-PD-1 treatment, neutralization of IL-8 in combination with checkpoint blockade is an attractive combination therapy approach.23
- Phase I trial of BMS-986253, an anti-IL-8 monoclonal antibody, in patients with metastatic or unresectable solid tumors. (2018) Collins J, et al. P3091. ASCO June 1-4. Chicago, IL.
Serum immune markers increased from baseline with combination lenvatinib and pembrolizumab treatment in patients who achieved response.24
- Biomarker results and preclinical rationale for combination lenvatinib and pembrolizumab in advanced endometrial carcinoma. (2018) Makker V, et al. P5597. ASCO June 1-5. Chicago, IL.
IL-8 biomarker guided precision medicine Phase1/2b immuno-oncology trial.25
- Phase 1b/2 study of nivolumab in combination with an anti–IL-8 monoclonal antibody, BMS-986253, in a biomarker-enriched population of patients with advanced cancer. (2018) Melero I, et al. P TPS3109. ASCO June 1-4. Chicago, IL.
OX-40 agonist in combination with Nivo or IPI Increases serum IFN-g and IP-10 (CXCL10) levels.26
- From bench to bedside: exploring OX40 receptor modulation in a phase 1/2a study of the OX40 costimulatory agonist BMS-986178 ± nivolumab (NIVO) or ipilimumab (IPI) in patients with advanced solid tumors. (2018) Wang R, et al. LB-127. AACR April 14-18. Chicago, IL.
PEGylated IL-10 (Pegilodecakin) induces sustained elevation of Th1 and Th2 cytokines in serum.27,28,29
- PEGylated IL-10 (pegilodecakin) induces systemic immune activation, CD8+ T cell invigoration and polyclonal T cell expansion in cancer patients. (2018) Naing A, et al. Cancer Cell. 2018 Nov 12;34(5):775-791.e3.
- Phase I study with PEGylated human IL-10 (AM0010) alone or in combination with anti-PD-1 or FOLFOX - immune biomarker update. (2017) Naing A, et al. SITC. Nov 9-11. National Harbor, MD.
- Safety, antitumor activity, and immune activation of pegylated recombinant human interleukin-10 (Am0010) in patients with advanced solid tumors. (2016) Naing A, et al. J Clin Oncol. Oct 10;34(29):3562-35569.
Four plasma proteins correlate with clinical benefit of Axl kinase inhibition that reverses suppression of immune responses in AML patients. 30
- The orally available selective Axl inhibitor BGB324 (bemcentinib) induces diversification of the immune repertoire and specific changes in plasma biomarker profiles. (2017) Loges S, et al. ASH Dec 9-12. Atlanta, GA.
Low baseline myeloid cell-associated serum proteins (M-CSF, IL-8, and IL-6) and high baseline IFNγ-inducible proteins (CXCL9,CXCL10, and TWEAK) were associated with longer OS.31
- Differential association of myeloid cell and IFN-γ associated proteins with clinical response to durvalumab treatment in urothelial bladder cancer. (2017) Guo X, et al. P32. SITC Nov 8-12. National Harbor, MD.
TruCulture immunoprofiling of antigen-stimulated blood has a variety of applications in I/O clinical trials.32,33,34
- Preclinical investigations and a first-in-human phase I trial of M4112, the first dual inhibitor of indoleamine 2,3-dioxygenase 1 and tryptophan 2,3-dioxygenase 2, in patients with advanced solid tumors. Naing A, et al. (2020) J ImmunoTher Cancer 2020;8:e000870. doi:10.1136/jitc-2020-000870
- Results of the phase I open label clinical trial SAKK 06/14 assessing safety of intravesical instillation of VPM1002BC, a recombinant mycobacterium Bacillus Calmette Guerin (BCG), in patients with non-muscle invasive bladder cancer and previous failure of conventional BCG therapy. (2020) Rentsch CA, et al. OncoImmunology. 2020 Apr 21;9:1, 1748981, DOI:10.1080/2162402X.2020.1748981.
- Identifying baseline immune-related biomarkers to predict clinical outcome of immunotherapy. (2017) Gnjatic S, et al. J Immunother Cancer. 2017 May 16;5:44.
Low baseline serum IFNγ is associated with improved OS upon subsequent immunotherapy with bavituximab + docetaxel treatment. 35
- IFNγ analysis in blood and tissue as a potential prognostic and/or predictive biomarker. (2017) Kallinteris NL, et al. P458. AACR April 1-5, Washington D.C.
Serum biomarker changes from baseline reflect nivolumab pharmacodynamics in the tumor microenvironment. 36
- Immunomodulatory activity of nivolumab in metastatic renal cell carcinoma. (2015) Choueiri TK, et al. Clin Cancer Res. 2016 Nov 15;22(22):5461-5471.
Dose-dependent urelumab exposures were associated with peripheral NK and T-cell activation and an increase in IFNγ-induced serum cytokines (CXCL9, CXCL10, MIP-1β, MCP-2). 37,38
- Urelumab alone or in combination with rituximab in patients with relapsed refractory B-cell lymphoma. (2020) Timmerman J, et al. Am J Hematol. 2020 May;95(5):510-520. doi: 10.1002/ajh.25757.
- Assessing the potential for enhanced antibody-dependent cell-mediated cytotoxicity by combining the CD137 antibody urelumab with rituximab or cetuximab in patients with refractory lymphoma or select advanced solid tumors. (2016) Segal NH, et al. P267 SITC. Nov 9-13. National Harbor, MD.
Dose-proportional increase in serum sIL-2Ra and IP-10 (CXCL10) with anti–LAG-3 + nivolumab treatment.39
- Initial experience administering BMS-986016, a monoclonal antibody that targets lymphocyte activation gene (LAG)–3, alone and in combination with nivolumab to patients with hematologic and solid malignancies. (2016) Evan JL, et al. P238. SITC Nov 9-13. National Harbor, MD.
Serum immune markers at baseline and on-therapy suggest preexisting adaptive immunity is associated with nivolumab induced tumor regression.40
- Markers of inflammation are associated with clinical outcomes in patients with metastatic renal cell carcinoma treated with nivolumab. (2015) Sznol M, et al. J Immunother Cancer. 2015 Nov 04; P197.
Treatment was associated with increased levels of peripheral Th1-associated cytokines and chemokines and an increase in CD8+TILs indicative of immune activation in patients with NSCLC. 41
- Safety and clinical activity of MEDI4736, an anti-programmed cell death-ligand 1 (PD-L1) antibody, in patients with non-small cell lung cancer (NSCLC). (2015) Rizvi NA, et al. J Clin Oncology 33, no. 15_suppl (May 20, 2015) 8032. DOI: 10.1200/jco.2015.33.15_suppl.8032
Serum biomarker changes from baseline reflect nivolumab pharmacodynamics in the tumor microenvironment. 42
- Immunomodulatory activity of nivolumab in metastatic renal cell carcinoma. (2016) Choueiri TK, et al. Clin Cancer Res. 2016 Nov 15;22(22):5461-5471. doi: 10.1158/1078-0432.CCR-15-2839.
Baseline serum immune-related biomarkers independent of tumor PD-L1 status are associated with nivolumab or docetaxel prognosis in patients with NSCLC2. 43
- Impact of baseline serum cytokines on survival in patients with advanced squamous non-small cell lung cancer treated with nivolumab or docetaxel: exploratory analyses from checkmate 063 and checkmate 017. (2016) Farsaci B, et al. Abstract #9025, Poster Board #348. ASCO June 3–7, 2016; Chicago, IL & #LB-072. AARC April 16-20, 2016. New Orleans, LA.
Serum immune markers at baseline and on-therapy suggest preexisting adaptive immunity is associated with nivolumab induced tumor regression. 44
- Markers of inflammation are associated with clinical outcomes in patients with metastatic renal cell carcinoma treated with nivolumab. (2015) Sznol M, et al. J ImmunoTher Cancer 2015, 3(Suppl 2):P197.
Innate and adaptive immune-related proteins quantified in plasma are increased transiently during treatment. 45,46
- MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer. (2014) Powles T, et al. Nature 515:558-562.
- Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. (2014) Herbst R, et al. Nature 515:563-567.
Select from our extensive menu of immune-related immunoassay panels, to generate invaluable Immuno-oncology biomarker data from routinely collected serum or plasma samples.