BB-10010: an active variant of human macrophage inflammatory protein-1 alpha with improved pharmaceutical properties

Blood. 1995 Dec 15;86(12):4400-8.


The stem cell inhibitor, macrophage inflammatory protein-1 alpha (MIP-1 alpha) or LD78, protects multipotent hematopoietic progenitors in murine models from the cytotoxic effects of chemotherapy. Clinical use of human MIP-1 alpha during chemotherapy could therefore lead to faster hematologic recovery and may allow dose intensification. We have also shown that human MIP-1 alpha causes the rapid mobilization of hematopoietic cells, suggesting an additional clinical use in peripheral blood stem cell transplantation. However, the clinical evaluation of human MIP-1 alpha is complicated by its tendency to associate and form high molecular weight polymers. We have produced a variant of rhMIP-1 alpha, BB-10010, carrying a single amino acid substitution of Asp26 > Ala, with a reduced tendency to form large polymers at physiologic pH and ionic strength. This greatly increases its solubility, facilitating its production and clinical formulation. We confirmed the potency of BB-10010 as a human MIP-1 alpha-like agonist in receptor binding, calcium mobilization, inhibition of colony formation, and thymidine suicide assays. The myeloprotective activity of BB-10010 was shown in a murine model of repeated chemotherapy using hydroxyurea. BB-10010 is therefore an ideal variant with which to evaluate the therapeutic potential of recombinant human MIP-1 alpha.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Biopolymers
  • Bone Marrow / drug effects
  • Bone Marrow Diseases / chemically induced
  • Bone Marrow Diseases / drug therapy
  • Calcium / metabolism
  • Cell Cycle / drug effects
  • Chemokine CCL3
  • Chemokine CCL4
  • Colony-Forming Units Assay
  • Growth Inhibitors / pharmacology
  • Hematopoietic Stem Cells / drug effects
  • Humans
  • Hydroxyurea / toxicity
  • Macrophage Inflammatory Proteins
  • Mice
  • Molecular Sequence Data
  • Monokines / chemistry
  • Monokines / genetics
  • Monokines / pharmacokinetics*
  • Monokines / pharmacology
  • Mutagenesis, Site-Directed
  • Point Mutation
  • Radiation Injuries, Experimental / drug therapy
  • Receptors, Chemokine*
  • Receptors, Cytokine / metabolism
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / pharmacokinetics*
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Solubility
  • Structure-Activity Relationship


  • Biopolymers
  • Chemokine CCL3
  • Chemokine CCL4
  • Growth Inhibitors
  • Macrophage Inflammatory Proteins
  • Monokines
  • Receptors, Chemokine
  • Receptors, Cytokine
  • Recombinant Fusion Proteins
  • macrophage inflammatory protein 1alpha receptor
  • Calcium
  • Hydroxyurea