Cellular immunotherapy for cancer

doi:10.1136/bmj.323.7324.1289

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Anne C Armstrong (aarmstrong@picr.man.ac.uk), clinical research fellow,
David Eaton, clinical research fellow,
Joanne C Ewing, clinical research fellow

Cancer Research Campaign Department of Medical Oncology, Paterson Institute of Cancer Research, Christie Hospital NHS Trust, Manchester M20 4BX

Correspondence to: A C Armstrong

Accepted 5 July 2001

During the past decade, our rapidly escalating understanding of immune surveillance and an appreciation of the mechanisms by which tumours escape its notice have led to promising new strategies against cancer. This paper reviews the concepts behind current research into cellular immunotherapy for cancer, presents data from clinical trials, and discusses the potential of this treatment as an adjunct to conventional modes of cancer treatment.

Methods

All three authors are involved in research into cellular immunotherapy and gene therapy. We searched PubMed and Medline databases using the terms “cancer vaccines,” “dendritic cells,” and “lymphocyte therapy.”

The rationale for cellular immunotherapy of cancer

The importance of the interaction between the immune system and cancer cells was recognised in the 1890s when William Coley used streptococcal cultures to treat patients with advanced sarcoma. These attempts to activate general immunity led to clinical responses. More recently, antibodies and T cells that identify tumour antigens have been isolated from patients with cancer. It is clear that the immune system is capable of recognising tumour cells.

Fig 1

Antitumour immune response. Dendritic cells capture antigens released by cancer cells. After intracellular processing, antigenic peptides are loaded onto major histocompatibility complex (MHC) molecules on the surface of the dendritic cell. Specific T cells encounter these MHC-peptide complexes in conjunction with a costimulatory signal. The activated T cells proliferate and secrete cytokines, resulting in the production of a cascade of immune effector cells (IL-2=interleukin 2; GM-CSF=granulocyte-macrophage colony stimulating factor)

Cellular immunotherapy consists of giving the patient cells that stimulate antitumour activity in the patient (tumour and dendritic cell vaccines) or that have intrinsic antitumour activity (autologous and allogeneic lymphocytes). The aim is to harness potent immunological weapons to destroy cancer cells.

The immune response to cancer

Cytotoxic T lymphocytes are one of the critical effector cells that are able to lyse tumour cells. Receptors on the surface of T cells recognise antigens …