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Related Experiment Videos

Histamine in cancer immunotherapy

K Hellstrand1, S Hermodsson, M Brune

  • 1Department of Virology, Sahlgren's University Hospital, Göteborg, Sweden.

Scandinavian Journal of Clinical and Laboratory Investigation
|May 1, 1997
PubMed
Summary

Histamine enhances immunotherapy by enabling natural killer (NK) cells to overcome cancer cell inhibition. This novel strategy shows promise in treating metastatic melanoma and acute myelogenous leukemia (AML), improving survival and preventing relapse.

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Area of Science:

  • Immunology
  • Oncology
  • Pharmacology

Background:

  • Interleukin-2 (IL-2) and interferon-alpha (IFN-alpha) activate natural killer (NK) cells for antitumor activity but have limited efficacy in human cancers.
  • Phagocytes at the tumor site can inhibit NK cell activity, reducing the effectiveness of these cytokines.
  • Histamine has been identified as a factor that can counteract this phagocyte-induced inhibition.

Purpose of the Study:

  • To investigate a novel strategy for enhancing immunotherapy efficacy using histamine in combination with IL-2 or IFN-alpha.
  • To determine if histamine can overcome phagocyte-mediated inhibition of NK cells in cancer treatment.
  • To evaluate the clinical outcomes of combining histamine with IL-2 or IFN-alpha in patients with neoplastic diseases.

Main Methods:

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  • In vitro studies demonstrated that histamine synergizes with IL-2 or IFN-alpha to induce NK cell-mediated killing of human tumor cells.
  • In vivo studies in tumor-bearing mice showed that histamine enhances IL-2- and IFN-alpha-induced tumor cell destruction.
  • Clinical trials involved administering histamine via subcutaneous injections alongside IL-2 or IFN-alpha to over 50 patients with various neoplastic diseases, including metastatic melanoma and acute myelogenous leukemia (AML).

Main Results:

  • In vitro and in vivo experiments confirmed that histamine enhances the antitumor activity of IL-2 and IFN-alpha by enabling NK cell function.
  • Pilot trials in metastatic melanoma suggest that the addition of histamine to IL-2 and IFN-alpha prolongs survival and induces regression of refractory tumors.
  • A trial in AML indicated that histamine and IL-2 protect patients against disease relapse, with histamine being well-tolerated in home-based treatment.

Conclusions:

  • Histamine represents a novel and effective adjuvant therapy for enhancing immunotherapy with IL-2 and IFN-alpha in human neoplasia.
  • The combination of histamine with IL-2 or IFN-alpha demonstrates significant potential in improving treatment outcomes for metastatic melanoma and preventing relapse in AML.
  • Histamine is a safe and well-tolerated agent, supporting its further investigation in controlled clinical trials for various cancers.