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

J Transl Med. 2010 Jul 23;8:71. doi: 10.1186/1479-5876-8-71.


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: NCT00349934.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antibodies, Neoplasm / immunology
  • Antigens, CD / adverse effects
  • Antigens, CD / immunology
  • Antigens, CD / pharmacology
  • Antigens, CD / therapeutic use*
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / immunology*
  • Breast Neoplasms / pathology
  • Cell Count
  • Drug Administration Schedule
  • Female
  • Humans
  • Immunity / immunology*
  • Immunotherapy*
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology
  • Lymphocyte Activation Gene 3 Protein
  • Middle Aged
  • Monocytes / cytology
  • Monocytes / drug effects
  • Neoplasm Metastasis
  • Paclitaxel / adverse effects
  • Paclitaxel / pharmacology
  • Paclitaxel / therapeutic use*
  • Remission Induction
  • Treatment Outcome


  • Antibodies, Neoplasm
  • Antigens, CD
  • Antineoplastic Agents
  • Paclitaxel
  • Lymphocyte Activation Gene 3 Protein
  • Lag3 protein, human
  • soluble LAG-3 protein, human

Associated data