15IN - Design of the ideal trial with immunotherapeutics

Date 29 September 2014
Event ESMO 2014
Session Cancer immunotherapy in breast cancer: Dream or reality?
Topics Breast Cancer, Metastatic
Cancer Immunology and Immunotherapy
Presenter Giuseppe Curigliano
Citation Annals of Oncology (2014) 25 (suppl_4): iv6-iv7. 10.1093/annonc/mdu292
Authors G. Curigliano
  • Medicine, Istituto Europeo di Oncologia, 20141 - Milano/IT

Abstract

Body

Abstract:

The basic concept of immunotherapy in cancer is to enable the immune system to identify neoplastic cells. Research on tumour associated antigens has identified a large collection of peptide epitopes that have been and are being used for vaccination of cancer patients. Several potential advantages of using peptide-based vaccines include 1) easy and relatively inexpensive production of synthetic peptides; 2) the easy administration of peptides in a clinical setting; 3) the possibility of treating only those patients whose tumours over-express the target antigens and 4) the availability of in vitro or ex vivo assays that can assess patients' immune response to vaccine epitopes. An ideal and successful vaccine should have: a target antigen on tumour cells to direct the immune response; a platform to present the vaccine-derived antigen to immune system; an adjuvant to enhance immune stimulation, and appropriate monitoring techniques. The design of a clinical trial in patient with breast cancer should identify the better population candidate to a vaccine trial and, primarily, the better antigen. In order to design a ‘second generation’ immunotherapy protocols we should highlight 3 issues: (a) the ability to initiate tumour-specific immunity, either directly by providing tumour associated antigens or indirectly, by favoring the cross-presentation of endogenous tumour antigens; (b) the capacity to recruit effector immune cells within the tumour site, by increasing tumour visibility; (c) the ability to preserve immune cell functionality within the tumour microenvironment through the subversion of immune-escape mechanisms. Cancer takes advantage of this ability to hide from the immune system by exploiting a series of immune escape mechanisms that were developed to avoid autoimmunity. Among these mechanisms are the hijacking of immune-cell–intrinsic checkpoints that are induced on T-cell activation. Blockade of one of these checkpoints, cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) or the programmed death 1 (PD-1) receptor, recently provided the first evidence of activity of an immune-modulation approach in the treatment of a solid tumour. The immune system remembers what it targets, so once the system is correctly activated, it may mediate a durable tumour response

Disclosure:

The author has declared no conflicts of interest.