T-cell-directed cancer vaccines

The melanoma model

Ena Wang, Giao Q. Phan, Francesco M. Marincola

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Significant advances in the understanding of the molecular basis for tumour/host interactions in humans have occurred in the last decade through studying patients with metastatic melanoma. This disease is characterised by its tendency to be modulated by immunologie factors. Furthermore, immunologie manipulation of the host with various systemic agents, in particular EL-2, frequently affects this natural phenomenon and can lead to complete rejection of cancer. By studying the cellular immunology occurring in patients undergoing immunotherapy, several tumour antigens (TA) and their epitopes recognised by human leukocyte antigen (HLA) class I-restricted cytotoxic T-lymphocytes (CTL) have been identified. Most of these TA are non-mutated molecules expressed by the majority of melanoma in vivo and most melanoma cell lines. In addition, unique minimal epitopic sequences play an immunodominant role in the context of specific HLA class I alleles. Since melanoma lesions from different patients often share expression of the same TA, and a minimal peptide sequence from a TA can cause immunologie changes in multiple patients, interest has grown in the development of TA-specific vaccines suitable for broad patient populations. Repeated in vitro stimulation of peripheral blood mononuclear cells (PBMC) with TA-derived epitopes can induce a high frequency of TA-reactive T-cells in melanoma patients. The same epitopes can also enhance TA-specific T-cell reactivity in vivo when administered subcutaneously in combination with Incomplete Freund's Adjuvant (IFA). Epitope-based vaccinations, however, have not shown strong clinical efficacy unless combined with IL-2 administration. Attempts to increase the efficacy of these vaccines have combined specialised antigen-presenting cells or the administration of whole TA through DNA- or RNA-based vaccines with the intention of increasing antigen presentation and processing. Save for scattered reports, however, the success of these approaches has been limited and T-cell-directed vaccination against cancer remains at a paradoxical standstill whereby anticancer immunisation can be induced but it is not sufficient, in most cases, to induce tumour regression. Using melanoma as the standard model for immunotherapy, we will review various methods of T-cell-directed vaccination, the monitoring and analysis of the resulting immune response, and several clinical trials in which cancer vaccines have successfully induced immunisation. 2001

Original languageEnglish
Pages (from-to)277-290
Number of pages14
JournalExpert Opinion on Biological Therapy
Volume1
Issue number2
Publication statusPublished - 2001
Externally publishedYes

Fingerprint

Cancer Vaccines
T-cells
Neoplasm Antigens
Melanoma
T-Lymphocytes
Epitopes
Immunization
Vaccination
Vaccines
Antigen Presentation
HLA Antigens
Immunotherapy
Tumors
Neoplasms
Immunology
Combined Vaccines
Cytotoxic T-Lymphocytes
Antigen-Presenting Cells
Allergy and Immunology
Interleukin-2

Keywords

  • Immune monitoring
  • Immunotherapy
  • Melanoma
  • Neoplasm
  • T-lymphocyte
  • Vaccines

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

Cite this

T-cell-directed cancer vaccines : The melanoma model. / Wang, Ena; Phan, Giao Q.; Marincola, Francesco M.

In: Expert Opinion on Biological Therapy, Vol. 1, No. 2, 2001, p. 277-290.

Research output: Contribution to journalArticle

Wang, E, Phan, GQ & Marincola, FM 2001, 'T-cell-directed cancer vaccines: The melanoma model', Expert Opinion on Biological Therapy, vol. 1, no. 2, pp. 277-290.
Wang, Ena ; Phan, Giao Q. ; Marincola, Francesco M. / T-cell-directed cancer vaccines : The melanoma model. In: Expert Opinion on Biological Therapy. 2001 ; Vol. 1, No. 2. pp. 277-290.
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