Harnessing NKT cells to promote T cell responses to vaccination  — ASN Events
  1. Schedule
  2. Session 10 - Autoimmunity/Cancer I
  3. Harnessing NKT cells to promote T cell responses to vaccination 

Harnessing NKT cells to promote T cell responses to vaccination  (#75)

Ian F Hermans 1
  1. Malaghan Institute of Medical Research, Wellington, New Zealand

Type 1 natural killer T (NKT) cells have the capacity to amplify adaptive immune responses by licensing antigen-presenting cells. Because both the T cell receptor and the antigen-presenting molecule, CD1d, are largely invariant, compounds that stimulate NKT cells can be thought of as immune adjuvants capable of universally eliciting T helper cell function. We are exploring this concept in the context of dendritic cell-based vaccines in cancer patients, while at the same time we have been assessing efficacy of simpler, tumour cell-based vaccines that harness NKT cells in a number of preclinical models of cancer1,2. We have also developed entirely synthetic vaccines consisting of peptides conjugated via self-immolative linkers to CD1d-binding NKT cell agonists3,4. Although capable of promoting T cell activity, full impact of NKT cell-adjuvanted vaccines in cancer treatment is likely to be in the context of strategies that relieve immunosuppression, such a removal of regulatory T cells, or combination with immune checkpoint blockade. Examples of successful combination therapies in preclinical models will be shown.

  1. Hunn, M. K., Farrand, K. J., Broadley, K. W. R., Weinkove, R., Ferguson, P., Miller, R. J., et al. (2012). Vaccination with irradiated tumor cells pulsed with an adjuvant that stimulates NKT cells is an effective treatment for glioma. Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, 18(23), 6446–6459. doi:10.1158/1078-0432.CCR-12-0704
  2. Gibbins, J. D., Ancelet, L. R., Weinkove, R., Compton, B. J., Painter, G. F., Petersen, T. R., & Hermans, I. F. (2014). An autologous leukemia cell vaccine prevents murine acute leukemia relapse after cytarabine treatment. Blood, 124(19), 2953–2963. doi:10.1182/blood-2014-04-568956
  3. Anderson, R. J., Tang, C.-W., Daniels, N. J., Compton, B. J., Hayman, C. M., Johnston, K. A., et al. (2014). A self-adjuvanting vaccine induces cytotoxic T lymphocytes that suppress allergy. Nature Chemical Biology, 10(11), 943–949. doi:10.1038/nchembio.1640
  4. Anderson, R.J., Compton, B.J., Tang, C., Authier-Hall, A., Hayman, C.M., Swinerd, G.W., et al (2015) NKT cell-dependent glycolipid-peptide vaccines with potent anti-tumour activity Chemical Science doi: 10.1039/C4SC03599B.