Can immunotherapy by gene transfer tip the balance against colorectal cancer?

Abstract

Gene therapy, in particular the transfer of genes encoding immunostimulatory molecules (cytokines and costimulatory molecules) as well as selectively cytotoxic enzymes and DNA vaccination, has the potential of enhancing cell mediated immune responses against tumours including those of colorectal origin. Genes can be transferred using viral vectors either to cultured tumour cells in vitro that can be returned to the patient as a "cancer vaccine", or directly to tumour cells in vivo. Vaccination with DNA constructs expressing specific tumour antigens characteristic of colorectal neoplasia can trigger immune recognition and destruction of tumour cells. The aim is to tip the balance from protumour to antitumour mechanisms by generating a local immune response and systemic antitumour immune memory to destroy metastases. Studies in murine models, combined with human studies, show that such approaches could become an adjunct to current treatments for human colorectal cancer in the near future.

Figure 1

Tipping the balance in colorectal cancer. A number of protumour mechanisms outweigh antitumour mechanisms and allow colorectal tumours to survive and proliferate. Gene therapy with cytokine, immunostimulatory or suicide (prodrug activating) gene transfer to tumour cells, or DNA vaccination, aims to tip the balance towards antitumour mechanisms and tumour rejection by enhancing antitumour cellular immune responses. Correction of immune deficiencies associated with the tumour could work in synergy with enhancement of antitumour immunity and many of the genes shown could apply to both sides of the balance.