Histamine in cancer immunotherapy

Abstract

A novel strategy for enhancing the efficacy of immunotherapy with interleukin-2 (IL-2) and interferon-α (IFN-α) in human neoplasia is presented. IL-2 and IFN-α are potent activators of the antitumour activity of natural killer (NK) cells but only rarely reduce the tumour burden in treated patients. Recent studies suggest that a reason why these cytokines are insufficiently effective in human cancer is that phagocytes inhibit the tumour-killing activity of NK cells at the site of the tumour. Histamine prevents the phagocyte-induced, NK cell-inhibiting signal; thus, histamine and IL-2 or histamine and IFN-α synergize to induce NK cell-mediated killing of human tumour cells in vitro. Further, treatment of tumour-bearing mice with histamine enhances IL-2- and IFN-α-induced destruction of NK cell-sensitive tumour cells in vivo.

More than 50 patients with neoplastic disease have been treated with histamine, given in subcutaneous injections, together with IL-2 or IFN-α. The results of two pilot trials in metastatic melanoma suggest that the addition of histamine to IL-2 and IFN-α prolongs survival time and induces regression of tumours, such as liver melanoma, which are otherwise considered refractory to immunotherapy. The results of a trial in acute myelogenous leukaemia (AML) suggest that histamine and IL-2 protects AML patients against relapse of leukaemic disease. Histamine is well tolerated: for example, AML patients in remission have treated themselves with histamine at home without supervision for a total of >300 weeks with only a handful of therapy-related hospital contacts. Controlled trials in melanoma and AML are under way to further investigate the putative benefit of histamine in neoplastic disease.

Key Words:

• histamine
• IFN-α
• IL-2
• immunotherapy
• NK cells

Additional information

Notes on contributors

U.-H. Mellqvist

Joyce Laing works in the Department of Child and Family Psychiatry, Playfield House, Cupar, Fife, and is a Consultant Art Therapist to Psychiatric Hospitals and Prisons and Chairwoman of the Scottish Society of Art and Psychology.