Research ArticleImmunotherapy

Targeting Intracellular Oncoproteins with Antibody Therapy or Vaccination

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Science Translational Medicine  07 Sep 2011:
Vol. 3, Issue 99, pp. 99ra85
DOI: 10.1126/scitranslmed.3002296

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The Tip of the Iceberg

As Titanic fans know, the largest mass of an iceberg hides under the water’s surface; having knowledge of the buried body might help sidestep tragic results. Antibody-based immunotherapy for cancer has faced a similar problem: Therapeutic antibodies were thought to have access only to molecules that appear on the cell surface, leaving a large intracellular treasure of potential cancer-specific therapeutic targets untapped. Now, Guo et al. show that proteins hidden within cells can be attacked by antibodies as well.

Guo et al. induced tumor regression in mice by introducing antibodies specific to three different intracellular proteins. Tumors targeted with unrelated antibodies produced no beneficial response. This tumor regression depended on the presence of immune B cells, which are responsible for antibody production, potentially by improving entry of the antibodies into the tumor cell. Moreover, vaccination with these intracellular proteins spurred production of specific antibodies by the host, which also led to tumor regression. These data suggest that antibody therapies be extended to include the rest of the iceberg—intracellular oncoproteins—which would vastly expand the repertoire of potential cancer-restricted targets and may help to circumvent tragic outcomes for patients.

Footnotes

  • * These authors contributed equally to this work.

  • Citation: K. Guo, J. Li, J. P. Tang, C. P. B. Tan, C. W. Hong, A. Q. O. Al-Aidaroos, L. Varghese, C. Huang, Q. Zeng, Targeting Intracellular Oncoproteins with Antibody Therapy or Vaccination. Sci. Transl. Med. 3, 99ra85 (2011).