Antibody-dependent and spontaneous lympholysis in urologic cancer patients

Ratliff, Timothy L.; McCool, Robert E.; Catàlona, William J.

doi:10.1038/bjc.1979.118

Cited by 5 publications

(3 citation statements)

References 17 publications

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“…These responses have been reported in carcinomas of the prostate, transitional cell carcinomas of the bladder, and granular cell carcinomas of the kidney, and generally are accepted as demonstrating immunologic responsiveness by the patient toward his tumor [ll]. Ratliff et al [12] reported that in Immunologic responsiveness of patients toward urologic tumors previously has been reported by our laboratory. These studies identified elevated levels of circulating immune complexes [ 131, specific cell-mediated immunity against homologous tumor extracts [ 141, and peripheral blood leukocytic subset alterations in prostatic cancer patients [15].…”

Section: Discussionsupporting

confidence: 56%

The effect of low‐dose cyclophosphamide and immunologic exposure upon growth of established dunning R‐3327‐G subline rat prostate adenocarcinomas

Rubenstein

Mw²,

Ra³

et al. 1985

The Prostate

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Utilizing the Dunning rat prostate adenocarcinoma, a low dose of cyclophosphamide (CY), 30 mg/kg, administered either alone or following diethylstilbestrol (DES) therapy, was as effective as higher levels of CY (100 mg/kg) in ability to initiate tumor regression. A lower dose (10 mg/kg) of CY was initially ineffective. Animals which had been injected with tumor an additional 10 days prior to initiation of CY treatment were apparently more responsive to this mode of chemotherapy. The effect of this additional 10 days of immunologic exposure supports the belief that the activity of CY is augmented by the presence of immunologic competence. All animals which responded favorably toward therapy utilizing CY, alone or in combination with DES, were similarly able to reject subsequent tumor challenges. It is thought that low-dose CY may reduce the immunosuppressive effects observed with higher levels and presumably preserve the helper T cell population necessary to mount secondary immune responses.

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Section: Discussionsupporting

confidence: 56%

The effect of low‐dose cyclophosphamide and immunologic exposure upon growth of established dunning R‐3327‐G subline rat prostate adenocarcinomas

Rubenstein

Mw²,

Ra³

et al. 1985

The Prostate

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“…In 1979, Herberman RG et al summarised in a review article [ 38 ] that NK activity had been found to be impaired in tumour-bearing mice and patients that had large tumour loads. In later years, more reports showed that the ADCC activity of NK cells was impaired in patients with cancer, including breast [ 39 ], gastric [ 40 ], esophageal [ 41 , 42 ], and urologic cancers [ 43 ] as well as leukemia [ 44 - 46 ] and myeloma [ 47 ]. In addition, NK activity can decline with age [ 48 ], which may contribute to higher incidence of cancer developed in elderly populations.…”

Section: Discussionmentioning

confidence: 99%

Natural killer cells are crucial for the efficacy of Icon (factor VII/human IgG1 Fc) immunotherapy in human tongue cancer

2010

BMC Immunol

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BackgroundIcon is a novel, dual neovascular- and cancer cell-targeting immunotherapeutic agent and has shown efficacy in the treatment of cancer, wet form macular degeneration and endometriosis. However, its underlying mechanism remains to be investigated. The objective of this study is to elucidate the mechanism of Icon immunotherapy in cancer using a squamous carcinoma human tongue cancer line TCA8113 in vitro and in vivo in severe combined immunodeficiency (SCID) mice.ResultsWe showed that Icon, as a chimeric factor VII and human IgG1 Fc immunoconjugate, could separately induce murine natural killer (NK) cells and activate complement to kill TCA8113 cancer cells in vitro via antibody dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). However, Icon-NK ADCC had a significantly stronger effect than that of Icon-CDC. Moreover, Icon could completely eradicate established human tongue tumour xenografts in vivo in the CB-17 strain of SCID mice that have functional NK cells at a normal level, whereas it was less effective in SCID/Beige mice that do not have functional NK cells.ConclusionsWe conclude that NK cells are crucial for the efficacy of Icon immunotherapy in the treatment of cancer. The results also suggest that impaired NK level/activity could contribute to the resistance to therapeutic antibodies that are currently under investigation in preclinical and clinical studies.

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“…A few years after the discovery of NK cells [21][22][23], it was found that NK cells could be impaired, observed as lower level/decreased activity in peripheral blood lymphocytes (PBL), by tumors in animals and cancer patients [24]. In later years, more reports showed that the ADCC activity of NK cells was impaired in patients with cancer [1,25,26], including head and neck [27,28], breast [29], gastric [30], esophageal [31,32], cervical [33] and urologic cancers [34] as well as leukemia [35][36][37] and myeloma [38]. In addition, NK activity could decline with age [39], which may contribute to and explain why higher incidence of cancer developed in elderly populations.…”

Section: Impairment Of Nk Cells In Cancer Patientsmentioning

confidence: 99%

Overcome the Impairment of NK Cells for Icon and Antibody Immunotherapy of Cancer

Hu¹

2013

JIBTVA

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Natural killer (NK) cells play an important role in innate immunity and in mediating antibody and Icon (an antibody-like factor VII/IgG1 Fc immunoconjugate, which, to our best knowledge, was the first therapeutic agent for dual targeting of both the tumor cells and tumor angiogenic endothelial cells) for cancer immunotherapy. However, a common yet often neglected observation and challenge in antibody immunotherapy is that NK cells are often impaired in cancer patients. Here we hypothesize that the impairment of NK cells significantly contributes to host resistance to antibody immunotherapy for cancer. In order for antibody and Icon to achieve their optimal therapeutic efficacy, we briefly reviewed the current strategies to enhance NK activity, including infusion of cytokines, vaccines or NK cells, and the use of dietary supplements. Moreover, from our point of view we identified some remaining challenges and propose to combine these NK-enhancing strategies with Icon or antibody to overcome NK impairment and ultimately to optimize the efficacy of Icon and antibody immunotherapy for cancer.

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Antibody-dependent and spontaneous lympholysis in urologic cancer patients

Cited by 5 publications

References 17 publications

The effect of low‐dose cyclophosphamide and immunologic exposure upon growth of established dunning R‐3327‐G subline rat prostate adenocarcinomas

The effect of low‐dose cyclophosphamide and immunologic exposure upon growth of established dunning R‐3327‐G subline rat prostate adenocarcinomas

Natural killer cells are crucial for the efficacy of Icon (factor VII/human IgG1 Fc) immunotherapy in human tongue cancer

Overcome the Impairment of NK Cells for Icon and Antibody Immunotherapy of Cancer

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