First-line chemoimmunotherapy in metastatic breast carcinoma: combination of paclitaxel and IMP321 (LAG-3Ig) enhances immune responses and antitumor activity | Brignone et al. Journal of Translational Medicine 2010 8 71 http content 8 1 71 RESEARCH JOURNAL OF TRANSLATIONAL MEDICINE Open Access First-line chemoimmunotherapy in metastatic breast carcinoma combination of paclitaxel and IMP321 LAG-3Ig enhances immune responses and antitumor activity 12 2 2 2 2 Chrystelle Brignone Maya Gutierrez Fawzia Mefti Etienne Brain Rosana Jarcau Frédérique Cvitkovic 2 3 4 s I z 1 1 1 Nabil Bousetta Jacques Medioni Joseph Gligorov Caroline Grygar Manon Marcu Frédéric Triebel 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 . 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 and 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. .
