Molecular Medicine Israel

Targeting Intracellular Oncoproteins with Antibody Therapy or Vaccination

Qi Zeng,  A*STAR Institute of Molecular and Cell Biology, Singapore. Sci. Transl. Med. DOI: 10.1126

Antibodies targeting intracellular proteins associated with cancer — oncoproteins — can halt tumor growth, so could become effective cancer therapies, according to research led by Qi Zeng of the A*STAR Institute of Molecular and Cell Biology, Singapore.

Despite the greater specificity of antibody-based therapies compared with chemotherapy, antibodies were considered too large to access intracellular proteins so were used to target extracellular proteins only.

Zeng and her colleagues, however, showed that antibodies targeting two intracellular oncoproteins expressed in melanoma cancer cells in wild-type mice effectively inhibited tumor growth and spread. The antibodies also triggered the animals’ own immune system, leading to further tumor regression.

The mechanism underlying this effect is unclear. The researchers suggest that the targeted proteins could be released from damaged cells or displayed on their surface by unusual secretion mechanisms. Another possibility is that the antibodies are taken up by cells and then induce cell death because the researchers found that B cells are required for the antibodies to be therapeutic. These cells may also enhance antibody uptake by cultured cancer cells.

“The ability to target intracellular oncoproteins could usher in a new era of tailor-made cancer vaccines,” says Zeng.

Article abstract

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