Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2015 May 21;3(2):420-8.
doi: 10.3390/vaccines3020420.

Integrating Immune Checkpoint Blockade with Anti-Neo/Mutated Antigens Reactivity to Increase the Clinical Outcome of Immunotherapy

Giorgio Parmiani  1   2 , Cristina Maccalli  3   4 , Michele Maio  5
Affiliations
Review

Integrating Immune Checkpoint Blockade with Anti-Neo/Mutated Antigens Reactivity to Increase the Clinical Outcome of Immunotherapy

Giorgio Parmiani et al. Vaccines (Basel). .

Abstract

Antibodies to immune checkpoints have entered the clinical arena and have been shown to provide a clinical benefit for metastatic melanoma and, possibly, for other tumors as well. In this review paper we summarize this therapeutic activity and underline the functional mechanisms that may be involved. Among them, we discuss the so far neglected role of tumor-associated antigens (TAAs) deriving from tumor somatic mutations and summarize the results of recent trials showing the immunogenic strength of such TAAs which can be specifically targeted by T cells activated by immune checkpoint antibodies. Finally we discuss new immunotherapy approaches that involve the combination of self/shared- or neo-TAAs-based vaccines and immune checkpoint blockade antibodies, to increase the clinical response of metastatic melanoma patients.

Keywords: immune checkpoint antibodies; melanoma immunotherapy; neo/mutated tumor antigens.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Khan S., Burt D.J., Ralph C., Thistlethwaite F.C., Hawkins R.E., Elkord E. Tremelimumab (Anti-CTLA4) mediates immune responses mainly by direct activation of T effector cells rather than by affecting T regulatory cells. Clin. Immunol. 2010;138:85–96. doi: 10.1016/j.clim.2010.09.011. - DOI - PubMed
    1. Cha E., Klinger M., Hou Y., Cummings C., Ribas A., Faham M., Fong L. Improved survival with T cell clonotype stability after anti-CTLA4 treatment in cancer patients. Sci. Transl. Med. 2014 doi: 10.1126/scitranslmed.3008211. - DOI - PMC - PubMed
    1. Peng W., Liu C., Xu C., Lou Y., Chen J., Yang Y., Yagita H., Overwijk W.W., Lizée G., Radvanyi L., et al. PD-1 blockade enhances T-cell migration to tumors by elevating IFN-γ-inducible chemokines. Cancer Res. 2012;72:5209–5218. doi: 10.1158/0008-5472.CAN-12-1187. - DOI - PMC - PubMed
    1. Curran M.A., Montalvo W., Yagita H., Allison J.P. PD-1 and CTLA-4 combination blockade expands infiltrating T cells and reduces regulatory T and myeloid cells within B16 melanoma tumors. Proc. Natl. Acad. Sci. USA. 2010;107:4275–4280. doi: 10.1073/pnas.0915174107. - DOI - PMC - PubMed
    1. Robert C., Schachter J., Long G.V., Arance A., Grob J.J., Mortier L., Daud A., Carlino M.S., McNeil C., Lotem M., et al. KEYNOTE-006 Investigators. Pembrolizumab versus ipilimumab in advanced melanoma. N. Engl. J. Med. 2015 doi: 10.1056/NEJMoa1503093. - DOI - PubMed