Old-School Chemotherapy in Immunotherapeutic Combination in Cancer, A Low-cost Drug Repurposed

Rasha Abu Eid, Ghazaleh Shoja E Razavi, Mikayel Mkrtichyan, John Janik, Samir N Khleif

Research output: Contribution to journalArticle

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Abstract

Cancer immunotherapy has proven to be a potent treatment modality. Although often successful in generating antitumor immune responses, cancer immunotherapy is frequently hindered by tumor immune-escape mechanisms. Among immunosuppressive strategies within the tumor microenvironment, suppressive immune regulatory cells play a key role in promoting tumor progression through inhibiting the effector arm of the immune response. Targeting these suppressive cells can greatly enhance antitumor immune therapies, hence augmenting a highly effective therapeutic antitumor response. Several approaches are being tested to enhance the effector arm of the immune system while simultaneously inhibiting the suppressor arm. Some of these approaches are none other than traditional drugs repurposed as immune modulators. Cyclophosphamide, an old-school chemotherapeutic agent used across a wide range of malignancies, was found to be a potent immune modulator that targets suppressive regulatory immune cells within the tumor microenvironment while enhancing effector cells. Preclinical and clinical findings have confirmed the ability of low doses of cyclophosphamide to selectively deplete regulatory T cells while enhancing effector and memory cytotoxic T cells within the tumor microenvironment. These immune effects translate to suppressed tumor growth and enhanced survival, evidence of antitumor therapeutic efficacy. This article discusses the reincarnation of cyclophosphamide as an immune modulator that augments novel immunotherapeutic approaches. Cancer Immunol Res; 4(5); 377-82. ©2016 AACR.

Original languageEnglish
Pages (from-to)377-382
Number of pages6
JournalCancer immunology research
Volume4
Issue number5
DOIs
Publication statusPublished - May 2016

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Drug Repositioning
Costs and Cost Analysis
Drug Therapy
Tumor Microenvironment
Cyclophosphamide
Neoplasms
Immunotherapy
Tumor Escape
Aptitude
Regulatory T-Lymphocytes
Therapeutics
Immunosuppressive Agents
Immune System
T-Lymphocytes
Growth

Keywords

  • Journal Article
  • Review

Cite this

Old-School Chemotherapy in Immunotherapeutic Combination in Cancer, A Low-cost Drug Repurposed. / Abu Eid, Rasha; Razavi, Ghazaleh Shoja E; Mkrtichyan, Mikayel; Janik, John; Khleif, Samir N.

In: Cancer immunology research, Vol. 4, No. 5, 05.2016, p. 377-382.

Research output: Contribution to journalArticle

Abu Eid, Rasha ; Razavi, Ghazaleh Shoja E ; Mkrtichyan, Mikayel ; Janik, John ; Khleif, Samir N. / Old-School Chemotherapy in Immunotherapeutic Combination in Cancer, A Low-cost Drug Repurposed. In: Cancer immunology research. 2016 ; Vol. 4, No. 5. pp. 377-382.
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abstract = "Cancer immunotherapy has proven to be a potent treatment modality. Although often successful in generating antitumor immune responses, cancer immunotherapy is frequently hindered by tumor immune-escape mechanisms. Among immunosuppressive strategies within the tumor microenvironment, suppressive immune regulatory cells play a key role in promoting tumor progression through inhibiting the effector arm of the immune response. Targeting these suppressive cells can greatly enhance antitumor immune therapies, hence augmenting a highly effective therapeutic antitumor response. Several approaches are being tested to enhance the effector arm of the immune system while simultaneously inhibiting the suppressor arm. Some of these approaches are none other than traditional drugs repurposed as immune modulators. Cyclophosphamide, an old-school chemotherapeutic agent used across a wide range of malignancies, was found to be a potent immune modulator that targets suppressive regulatory immune cells within the tumor microenvironment while enhancing effector cells. Preclinical and clinical findings have confirmed the ability of low doses of cyclophosphamide to selectively deplete regulatory T cells while enhancing effector and memory cytotoxic T cells within the tumor microenvironment. These immune effects translate to suppressed tumor growth and enhanced survival, evidence of antitumor therapeutic efficacy. This article discusses the reincarnation of cyclophosphamide as an immune modulator that augments novel immunotherapeutic approaches. Cancer Immunol Res; 4(5); 377-82. {\circledC}2016 AACR.",
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