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Molecular Medicine

, Volume 12, Issue 11–12, pp 345–346 | Cite as

CD38 as a Therapeutic Target

  • George T Stevenson
Proceedings

Abstract

The CD38 molecule is well represented on cell surfaces in many cases of a variety of lymphoid tumors, notably multiple myeloma, AIDS-associated lymphomas, and post-transplant lymphoproliferations. As such, this molecule is a promising target for antibody therapy. After early disappointments, improved anti-CD38 antibodies of strong cytolytic potential have been described by 3 groups. First, a human IgG monoclonal anti-CD38 antibody raised in mice transgenic for human Ig has been found to induce potent complement and cellular cytotoxicities against both myeloma cell lines and fresh harvests from myeloma marrow and leukemic blood. This antibody also exhibits the singular property of inhibiting the CD38 cyclase activity. Second, a series of CD38-specific human antibodies, with high affinities and high ADCC activities against cell lines and primary cultures of myeloma, has been selected from a unique phage-display library. Finally, to enhance specificity for myeloma cells, bispecific domain antibodies targeting both CD38 and CD138 have been developed. As they lack any Fc module, these constructs rely on cytotoxicity for delivering a toxin to tumor cells. The list of candidate CD38-bearing neoplasms as targets for these antibody constructs can now be expanded to include acute promyelocytic leukemia, and possibly other myeloid leukemias, in which surface CD38 can be induced by retinoid treatment. One caveat here is that evidence has been produced to suggest that CD38 promotes pulmonary manifestations of the hazardous retinoic acid syndrome.

References

  1. 1.
    Deaglio S, Mehta K, Malavasi F. (2001) Human CD38: a (r)evolutionary story of enzymes and receptors. Leuk. Res. 25:1–12.CrossRefGoogle Scholar
  2. 2.
    Chan CS, Wormsley SB, Pierce LE, Peter JB, Schechter GP. (1990) B-cell surface phenotypes of proliferating myeloma cells: target antigens for immunotherapy. Am. J. Hematol. 33:101–9.CrossRefGoogle Scholar
  3. 3.
    Hoffmann C et al. (2005) AIDS-related B-cell lymphoma (ARL): correlation of prognosis with differentiation profiles assessed by immunophenotyping. Blood. 106:1762–9.CrossRefGoogle Scholar
  4. 4.
    Rochford R, Hobbs MV, Garnier JL, Cooper NR, Cannon MJ. (1993) Plasmacytoid differentiation of Epstein-Barr virus-transformed B cells in vivo is associated with reduced expression of viral latent genes. Proc. Natl. Acad. Sci. U. S. A. 90:352–6.CrossRefGoogle Scholar
  5. 5.
    Stevenson FK et al. (1991) Preliminary studies for an immunotherapeutic approach to the treatment of human myeloma using chimeric anti-CD38 antibody. Blood. 77:1071–9.PubMedGoogle Scholar
  6. 6.
    Ojo E, Wigzell H. (1978) Natural killer cells may be the only cells in normal mouse lymphoid cell populations endowed with cytolytic ability for antibody-coated tumor target cells. Scand. J. Immunol. 7:297–306.CrossRefGoogle Scholar
  7. 7.
    Verfaillie CM, Miller JS. (1994) CD34+/CD33− cells reselected from macrophage inflammatory protein 1 alpha+interleukin-3-supplemented “stroma-noncontact” cultures are highly enriched for long-term bone marrow culture initiating cells. Blood. 84:1442–9.PubMedGoogle Scholar
  8. 8.
    Goldmacher VS et al. (1994) Anti-CD38-blocked ricin: an immunotoxin for the treatment of multiple myeloma. Blood. 84:3017–25.PubMedGoogle Scholar
  9. 9.
    Mehta K, Ocanas L, Malavasi F, Marks JW, Rosenblum MG. (2004) Retinoic acid-induced CD38 antigen as a target for immunotoxin-mediated killing of leukemia cells. Mol. Cancer Ther. 3:345–52.PubMedGoogle Scholar
  10. 10.
    Gao Y, Camacho LH, Mehta K. (2006) Retinoic acid-induced CD38 antigen promotes leukemia cells attachment and interferon-γ/interleukin-1β-dependent apoptosis of endothelial cells: Implications in the etiology of retinoic acid syndrome. Leuk. Res. in press.Google Scholar

Copyright information

© Feinstein Institute for Medical Research 2006

Authors and Affiliations

  1. 1.Tenovus LaboratorySouthampton University HospitalsSouthamptonUK

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