Depletion of Tregs in vivo: a promising approach to enhance antitumor immunity without autoimmunity

Abstract

Evaluation of: Rech AJ, Mick R, Martin S et al. CD25 blockade depletes and selectively reprograms regulatory T cells in concert with immunotherapy in cancer patents. Sci. Transl. Med. 4(134), 134ra62 (2012). Tregs are involved in the maintenance of immunological self-tolerance. Recent studies have revealed that Tregs suppress antitumor immunity and that they are major obstacles for cancer immunotherapy. Various approaches have been carried out to cancel immunological suppression by Tregs in clinical settings; however, side effects such as autoimmunity occurred and expected antitumor effects were not achieved. In a recent study, Rech et al. evaluated daclizumab, a US FDA-approved humanized anti-CD25 antibody, for regulation of Treg cells in a peptide vaccination trial of breast cancer patients. Daclizumab caused long-lasting depletion of CD25⁺ Tregs, reprogramming of CD25⁺ Tregs, and enhancement of antipeptide immune response. Of note, major autoimmune responses were not observed in daclizumab-treated patients. This study provides a possible safe and promising approach to regulate Tregs in cancer vaccine therapy.

KEYWORDS::

• anti-CD25 antibody
• daclizumab
• immunotherapy
• Treg

Financial & competing interests disclosure

This work was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (grant numbers 16209013, 17016061 and 15659097) for Practical Application Research from the Japan Science and Technology Agency, and for Cancer Research (15-17 and 19-14) from the Ministry of Health, Labor and Welfare of Japan, Ono Cancer Research Fund (to N Sato) and Takeda Science Foundation (to Y Hirohashi). This work was supported in part by the National Cancer Center Research and Development Fund (23-A-44). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This work was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (grant numbers 16209013, 17016061 and 15659097) for Practical Application Research from the Japan Science and Technology Agency, and for Cancer Research (15-17 and 19-14) from the Ministry of Health, Labor and Welfare of Japan, Ono Cancer Research Fund (to N Sato) and Takeda Science Foundation (to Y Hirohashi). This work was supported in part by the National Cancer Center Research and Development Fund (23-A-44). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.