Immune correlates of talactoferrin alfa in biopsied tumor of relapsed/refractory metastatic non-small cell lung cancer patients

Jonathan Riess, Nupur Bhattacharya, Kim R M Blenman, Joel W. Neal, Gloria Hwang, Philippe Pultar, Melanie San-Pedro Salcedo, Edgar Engleman, Peter P. Lee, Rajesh Malik, Heather A. Wakelee

Research output: Contribution to journalArticle

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Abstract

Context: Talactoferrin alfa (TLF) is a unique recombinant form of human lactoferrin. The hypothesized mechanism of action involves TLF binding to the intestinal endothelium inducing dendritic cell maturation and cytokine release leading to infiltration of tumor with monocytes and T-lymphocytes and inhibition of tumor growth. Objective: Based on promising phase II trial results, this correlative study was undertaken to examine immune mechanism of action of TLF in metastatic non-small cell lung cancer (NSCLC) patients. Methods: Talactoferrin was administered orally at 1.5g bid weeks 1-12 with 2 weeks off on a 14-week cycle. Enrolled patients had a pathologic diagnosis of NSCLC previously treated with at least two lines of systemic treatment. Patients had core biopsy of tumor before initiation of talactoferrin and at week 7 on TLF. Flow cytometry and quantitative immunohistochemistry for immune correlates were performed on the biopsied specimens. Results: Four patients with metastatic NSCLC were enrolled. The trial was halted pre-maturely in light of negative phase III trial results. For the two patients who had repeat on-treatment tumor biopsies, a consistent increase in monocytes as a percentage of total immune cells was observed. Otherwise, no clear trend of increase or decrease was observed in any other immune cell parameters compared to matched patient pre-treatment biopsies. Conclusion: Repeat biopsies for immune correlates by flow cytometry and quantitative immunohistochemistry in NSCLC patients are feasible. In the few patients sampled before trial closure, increased monocytes as a total percentage of the immune cell population within tumor was observed in response to TLF.

Original languageEnglish (US)
Pages (from-to)182-186
Number of pages5
JournalImmunopharmacology and Immunotoxicology
Volume36
Issue number2
DOIs
StatePublished - Apr 2014

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Non-Small Cell Lung Carcinoma
Refractory materials
Tumors
Cells
Biopsy
Neoplasms
Flow cytometry
Monocytes
Flow Cytometry
Immunohistochemistry
Lactoferrin
T-cells
talactoferrin alfa
Infiltration
Dendritic Cells
Endothelium
Cytokines
Therapeutics
T-Lymphocytes
Growth

Keywords

  • Clinical trial
  • Immune correlates
  • Immunotherapy
  • NSCLC
  • Repeat biopsy

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Pharmacology
  • Toxicology

Cite this

Immune correlates of talactoferrin alfa in biopsied tumor of relapsed/refractory metastatic non-small cell lung cancer patients. / Riess, Jonathan; Bhattacharya, Nupur; Blenman, Kim R M; Neal, Joel W.; Hwang, Gloria; Pultar, Philippe; San-Pedro Salcedo, Melanie; Engleman, Edgar; Lee, Peter P.; Malik, Rajesh; Wakelee, Heather A.

In: Immunopharmacology and Immunotoxicology, Vol. 36, No. 2, 04.2014, p. 182-186.

Research output: Contribution to journalArticle

Riess, J, Bhattacharya, N, Blenman, KRM, Neal, JW, Hwang, G, Pultar, P, San-Pedro Salcedo, M, Engleman, E, Lee, PP, Malik, R & Wakelee, HA 2014, 'Immune correlates of talactoferrin alfa in biopsied tumor of relapsed/refractory metastatic non-small cell lung cancer patients', Immunopharmacology and Immunotoxicology, vol. 36, no. 2, pp. 182-186. https://doi.org/10.3109/08923973.2013.864671
Riess, Jonathan ; Bhattacharya, Nupur ; Blenman, Kim R M ; Neal, Joel W. ; Hwang, Gloria ; Pultar, Philippe ; San-Pedro Salcedo, Melanie ; Engleman, Edgar ; Lee, Peter P. ; Malik, Rajesh ; Wakelee, Heather A. / Immune correlates of talactoferrin alfa in biopsied tumor of relapsed/refractory metastatic non-small cell lung cancer patients. In: Immunopharmacology and Immunotoxicology. 2014 ; Vol. 36, No. 2. pp. 182-186.
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abstract = "Context: Talactoferrin alfa (TLF) is a unique recombinant form of human lactoferrin. The hypothesized mechanism of action involves TLF binding to the intestinal endothelium inducing dendritic cell maturation and cytokine release leading to infiltration of tumor with monocytes and T-lymphocytes and inhibition of tumor growth. Objective: Based on promising phase II trial results, this correlative study was undertaken to examine immune mechanism of action of TLF in metastatic non-small cell lung cancer (NSCLC) patients. Methods: Talactoferrin was administered orally at 1.5g bid weeks 1-12 with 2 weeks off on a 14-week cycle. Enrolled patients had a pathologic diagnosis of NSCLC previously treated with at least two lines of systemic treatment. Patients had core biopsy of tumor before initiation of talactoferrin and at week 7 on TLF. Flow cytometry and quantitative immunohistochemistry for immune correlates were performed on the biopsied specimens. Results: Four patients with metastatic NSCLC were enrolled. The trial was halted pre-maturely in light of negative phase III trial results. For the two patients who had repeat on-treatment tumor biopsies, a consistent increase in monocytes as a percentage of total immune cells was observed. Otherwise, no clear trend of increase or decrease was observed in any other immune cell parameters compared to matched patient pre-treatment biopsies. Conclusion: Repeat biopsies for immune correlates by flow cytometry and quantitative immunohistochemistry in NSCLC patients are feasible. In the few patients sampled before trial closure, increased monocytes as a total percentage of the immune cell population within tumor was observed in response to TLF.",
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AU - Neal, Joel W.

AU - Hwang, Gloria

AU - Pultar, Philippe

AU - San-Pedro Salcedo, Melanie

AU - Engleman, Edgar

AU - Lee, Peter P.

AU - Malik, Rajesh

AU - Wakelee, Heather A.

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N2 - Context: Talactoferrin alfa (TLF) is a unique recombinant form of human lactoferrin. The hypothesized mechanism of action involves TLF binding to the intestinal endothelium inducing dendritic cell maturation and cytokine release leading to infiltration of tumor with monocytes and T-lymphocytes and inhibition of tumor growth. Objective: Based on promising phase II trial results, this correlative study was undertaken to examine immune mechanism of action of TLF in metastatic non-small cell lung cancer (NSCLC) patients. Methods: Talactoferrin was administered orally at 1.5g bid weeks 1-12 with 2 weeks off on a 14-week cycle. Enrolled patients had a pathologic diagnosis of NSCLC previously treated with at least two lines of systemic treatment. Patients had core biopsy of tumor before initiation of talactoferrin and at week 7 on TLF. Flow cytometry and quantitative immunohistochemistry for immune correlates were performed on the biopsied specimens. Results: Four patients with metastatic NSCLC were enrolled. The trial was halted pre-maturely in light of negative phase III trial results. For the two patients who had repeat on-treatment tumor biopsies, a consistent increase in monocytes as a percentage of total immune cells was observed. Otherwise, no clear trend of increase or decrease was observed in any other immune cell parameters compared to matched patient pre-treatment biopsies. Conclusion: Repeat biopsies for immune correlates by flow cytometry and quantitative immunohistochemistry in NSCLC patients are feasible. In the few patients sampled before trial closure, increased monocytes as a total percentage of the immune cell population within tumor was observed in response to TLF.

AB - Context: Talactoferrin alfa (TLF) is a unique recombinant form of human lactoferrin. The hypothesized mechanism of action involves TLF binding to the intestinal endothelium inducing dendritic cell maturation and cytokine release leading to infiltration of tumor with monocytes and T-lymphocytes and inhibition of tumor growth. Objective: Based on promising phase II trial results, this correlative study was undertaken to examine immune mechanism of action of TLF in metastatic non-small cell lung cancer (NSCLC) patients. Methods: Talactoferrin was administered orally at 1.5g bid weeks 1-12 with 2 weeks off on a 14-week cycle. Enrolled patients had a pathologic diagnosis of NSCLC previously treated with at least two lines of systemic treatment. Patients had core biopsy of tumor before initiation of talactoferrin and at week 7 on TLF. Flow cytometry and quantitative immunohistochemistry for immune correlates were performed on the biopsied specimens. Results: Four patients with metastatic NSCLC were enrolled. The trial was halted pre-maturely in light of negative phase III trial results. For the two patients who had repeat on-treatment tumor biopsies, a consistent increase in monocytes as a percentage of total immune cells was observed. Otherwise, no clear trend of increase or decrease was observed in any other immune cell parameters compared to matched patient pre-treatment biopsies. Conclusion: Repeat biopsies for immune correlates by flow cytometry and quantitative immunohistochemistry in NSCLC patients are feasible. In the few patients sampled before trial closure, increased monocytes as a total percentage of the immune cell population within tumor was observed in response to TLF.

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