Chemoimmunotherapy with cyclophosphamide and bestatin in experimental metastasis in mice

Fuminori Abe, Mark Schneider, Paul L. Black, James E Talmadge

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Bestatin has significant therapeutic activity (even following oral administration) for the treatment of metastatic disease, an activity which is limited by tumor burden. Therefore, the therapeutic potential of bestatin was examined in combination with chemotherapy to determine if there is additive activity for heavy tumor burdens. Bestatin significantly increased therapeutic activity and decreased the myelotoxicity of cyclophosphamide following a single injection of cyclophosphamide or split daily doses. In immune function studies, in tumor-bearing antimals, bestatin increased the number of colony-forming units (granulocyte-macrophage) (CFU) and alveolar macrophage tumoricidal activity. However, when bestatin was combined with cyclophosphamide, which depressed bone marrow and macrophage activity, it did not show apparent augmentation of macrophage and NK cell activity, but did significantly increase bone marrow CFU activity. Thus, in combined chemoimmunotherapy, bestatin appears to enhance therapeutic activity by accelerating the recovery of hematopoiesis. We suggest, therefore, that a combination chemotherapy protocol, with oral bestatin, may facilitate myelorestoration following aggressive chemotherapy. The majority of biological response modifiers require parental administration; thus, the identification of an orally active, synthetic immunoaugmenting agent with a defined receptor is of particular interest.

Original languageEnglish (US)
Pages (from-to)231-236
Number of pages6
JournalCancer Immunology Immunotherapy
Volume29
Issue number4
DOIs
StatePublished - Aug 1 1989

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Cyclophosphamide
Neoplasm Metastasis
Combination Drug Therapy
Tumor Burden
Bone Marrow
Macrophages
Therapeutics
Granulocyte-Macrophage Progenitor Cells
Hematopoiesis
Alveolar Macrophages
Immunologic Factors
ubenimex
Natural Killer Cells
Oral Administration
Drug Therapy
Injections
Neoplasms

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research

Cite this

Chemoimmunotherapy with cyclophosphamide and bestatin in experimental metastasis in mice. / Abe, Fuminori; Schneider, Mark; Black, Paul L.; Talmadge, James E.

In: Cancer Immunology Immunotherapy, Vol. 29, No. 4, 01.08.1989, p. 231-236.

Research output: Contribution to journalArticle

Abe, Fuminori ; Schneider, Mark ; Black, Paul L. ; Talmadge, James E. / Chemoimmunotherapy with cyclophosphamide and bestatin in experimental metastasis in mice. In: Cancer Immunology Immunotherapy. 1989 ; Vol. 29, No. 4. pp. 231-236.
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