First-line chemoimmunotherapy in metastatic breast carcinoma: Combination of paclitaxel and IMP321 (LAG-3Ig) enhances immune responses and antitumor activity

  • C. B
  • M. G
  • F. M
  • et al.
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Abstract

Background: IMP321 is a recombinant soluble LAG-3Ig fusion protein that binds to MHC class II with high avidity and mediates APC and then antigen-experienced memory CD8+ T cell activation. We report clinical and biological results of a phase I/II in patients with metastatic breast carcinoma (MBC) receiving first-line paclitaxel weekly, 3 weeks out of 4.Methods: MBC patients were administered one dose of IMP321 s.c. every two weeks for a total of 24 weeks (12 injections). The repeated single doses were administered the day after chemotherapy at D2 and D16 of the 28-day cycles of paclitaxel (80 mg/m2 at D1, D8 and D15, for 6 cycles). Blood samples were taken 13 days after the sixth and the twelfth IMP321 injections to determine sustained APC, NK and memory CD8 T cell responses.Results: Thirty MBC patients received IMP321 in three cohorts (doses: 0.25, 1.25 and 6.25 mg). IMP321 induced both a sustained increase in the number and activation of APC (monocytes and dendritic cells) and an increase in the percentage of NK and long-lived cytotoxic effector-memory CD8 T cells. Clinical benefit was observed for 90% of patients with only 3 progressors at 6 months. Also, the objective tumor response rate of 50% compared favorably to the 25% rate reported in the historical control group.Conclusions: The absence of toxicity and the demonstration of activity strongly support the future development of this agent for clinical use in combined first-line regimens.Trial registration: ClinicalTrials.gov NCT00349934. © 2010 Brignone et al; licensee BioMed Central Ltd.

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C., B., M., G., F., M., E., B., R., J., F., C., … F., T. (2010). First-line chemoimmunotherapy in metastatic breast carcinoma: Combination of paclitaxel and IMP321 (LAG-3Ig) enhances immune responses and antitumor activity. Journal of Translational Medicine. F. Triebel, Immutep S.A., 2 rue Jean Rostand, Orsay, 91893, France. E-mail: ftriebel@immutep.com: BioMed Central Ltd. (Floor 6, 236 Gray’s Inn Road, London WC1X 8HB, United Kingdom). Retrieved from http://www.translational-medicine.com/content/8/1/71

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