Immunotherapy for gastrointestinal cancer: current status and strategies for improving efficacy

Abstract

Background: Despite improvement in conventional strategies for treating gastrointestinal (GI) carcinoma, large numbers of patients still suffer from incurable or progressive disease. Objective: Here we consider the prospects for circumventing limitations and maximising the efficacy of different immunotherapies. Methods: We summarise different cancer vaccines and targeted drugs and highlight the scientific rationale of using immunotherapy for targeting GI cancers, in addition to the potential strategies for improving immunotherapeutic efficacy. Results/conclusion: Many cancer vaccines and antibody-directed therapies have been tested in early phase clinical trials and demonstrated proof of concept and safety. As yet few have been properly evaluated for clinical efficacy; although adoptive transfer of tumour-associated-antigen-specific T cells has shown dramatic clinical responses in some patients. The recognition of a role for T regulatory cells in limiting anti-tumour immunity has provided momentum for developing strategies to over-ride such immunoinhibitory effects. There is some evidence that conventional therapies may work by influencing these negative factors and allowing expression of immune control mechanisms. An important developing area for clinical evaluation is the testing of combined conventional and immunotherapeutic modalities which may provide for synergy; thereby circumventing the limitations of individualised treatments and generating additional clinical benefits.

Keywords::

• colorectal cancer
• combination therapy
• gastrointestinal cancer
• immunotherapy
• T regulatory cells

Acknowledgement

The authors' research is principally supported by Cancer Research UK.