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


CONCLUSIONS
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.
Department of Medicine, Division of Oncology, Stanford University School of Medicine, Stanford, CA, USA .
Jonathan W
JW
Riess
Nupur
N
Bhattacharya
Kim R M
KR
Blenman
Joel W
JW
Neal
Gloria
G
Hwang
Philippe
P
Pultar
Melanie
M
San-Pedro Salcedo
Edgar
E
Engleman
Peter P
PP
Lee
Rajesh
R
Malik
Heather A
HA
Wakelee
D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology*; D005260:Female; D006801:Humans; D007781:Lactoferrin / Q000276:immunology*; D008175:Lung Neoplasms / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000276:immunology*
C515276:talactoferrin alfa; D007781:Lactoferrin