Basic research efforts focussing on angiogenesis as a target for cancer therapeutics have yet to bear fruit. Of the 58 molecules in development, 46 are still at preclinical stages. One of the most advanced class of angiogenesis related therapies, endostatin, is described earlier in this edition of TherapeuticAdvances. A second candidate, CM101 (also known as GBS toxin), has also been described in the literature. CM101 is a polysaccharide isolated from the culture medium of Group B streptococcus, a microbe known to cause respiratory distress in neonates. This is thought to occur through it's binding to a receptor whose expressed becomes repressed very shortly after birth. In 1993 it was shown that CM101 can inhibit tumor growth in mice suggesting that receptor expression is reinduced under neoplastic conditions. The mechanism of action was related to a destruction of tumor blood vessels subsequent to local perivascular inflammation. Following successful preclinical studies CM101 was tested in the clinic and out of 15 patients, 5 showed tumor reduction or stabilization. One potential problem with anti-angiogenic molecules is that they could prevent wound healing. This is not the case with CM101 and adverse effects related to treatment appeared to be inflammatory in nature. Despite these adverse effects, CM101 appears to be a selective and safe therapeutic candidate. Most recently, a gene encoding a transmembrane protein that interacts with CM101 was isolated from a sheep lung endothelial cell cDNA library. The gene, termed sp55, encodes a 495-amino acid polypeptide. COS-7 cells transfected with a vector containing sp55 express the SP55 protein and bound CM101 in a concentration-dependent manner. Stably transfected CHO cells also bound CM101. The corresponding human gene, hp59, was isolated from a human fetal lung cDNA library and had a predicted identity to SP55 of 86% over 495 amino acids. HP59 protein was shown by immunohistochemistry to be present in the pathological tumor vasculature of the lung, breast, colon, and ovary, but not in the normal vasculature, suggesting that the protein may be critical to pathological angiogenesis. The hp59 gene and/or the HP59 protein was not expressed in a variety of normal tissues, but was significantly expressed in human fetal lung, consistent with the pathophysiology of Group B streptococcus infections in neonates. Mice immunized with HP59 and SP55 peptides showed significant attenuation of tumor growth. Immunization effectively inhibited both the tumor angiogenesis and vasculogenesis processes, as evidenced by lack of both HP59- and CD34-positive vessels. These results and the immunohistochemistry data suggest a therapeutic potential for the CM101 target protein HP59 both as a drug target and as a vaccine against pathoangiogenesis. Collaboration with this group should allow for accelerated development of synthetic HP59 ligands. Of more general interest CM101 has shown dramatic effects in models of spinal chord injury almost completely preventing paralysis following acute treatment, and HP59-related molecules may be indicated for multiple indications.