Histamine in cancer immunotherapy.
A novel strategy for enhancing the efficacy of immunotherapy with interleukin-2 (IL-2) and interferon-alpha (IFN-alpha) in human neoplasia is presented. IL-2 and IFN-alpha 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-alpha 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-alpha-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-alpha. The results of two pilot trials in metastatic melanoma suggest that the addition of histamine to IL-2 and IFN-alpha 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.
Hellstrand
K
K
Department of Virology, Sahlgren's University Hospital, Göteborg, Sweden.
Hermodsson
S
S
Brune
M
M
Naredi
P
P
Carneskog
J
J
Mellqvist
U H
UH
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D006632:Histamine / Q000627:therapeutic use*; D006801:Humans; D016233:Immunotherapy, Active / Q000379:methods*
D000970:Antineoplastic Agents; D006632:Histamine