Augmentation of specific immune response against a syngeneic SV40-induced sarcoma in mice by depletion of suppressor T cells with cyclophosphamide

Glaser, Moshe

doi:10.1016/0008-8749(79)90128-x

Cited by 50 publications

(24 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the Berd et al 1984). For example suppressor T-cells are known to be specifically sensitive to CY (Rollinghof et al 1977 ;Glaser 1979 ;North 1982). It has been reported that elimination of suppressor T-cells by an injection of CY prior to sensitization leads to an augmentation of delayed-type hypersensitivity (Askenase et al 1975;Mitsuoka et al 1976; Thomson et al 1983 ;Bovbjerg et al 1986).…”

Section: Discussionmentioning

confidence: 99%

Antitumor activity of cyclophosphamide and lipopolysaccharide in tumor-bearing mice pretreated with BCG.

Sato

Itô

Abé

et al. 1987

Tohoku J. Exp. Med.

View full text Add to dashboard Cite

of Cyclophosphamide and Lipopolysaccharide in TumorBearing Mice Pretreated with BOG. Tohoku J. exp. Med., 1987, 153 (2), [151][152][153][154][155][156][157][158][159][160] Antitumor effects of cyclophosphamide (CY) and lipopolysaccharide (LPS) were investigated in BCG-treated mice. C3H/He mice and CDF1 mice were injected with BCG and were inoculated subcutaneously with syngeneic mouse hepatoma and mastocytoma P815 respectively. A subsequent injection of LPS caused hemorrhagic necrosis and retarded growth of tumor. When mice were treated with LPS plus suboptimal dose of CY, tumor growth was retarded and survival time was prolonged. The antitumor effects were more remarkable when mice were treated with CY prior to the injection of LPS. Without BCG pretreatment, LPS showed no antitumor activity in mice. Sera from mice treated with BCG plus PLS was cytotoxic for cultured tumor cells. However treatment of mice with CY did not increase the in vitro cytotoxicity. In this experimental condition, CY had no effect on delayed type hypersensitivity when evaluated by the footpad reaction to purified protein derivative (PPD). These results seem to indicate that the antitumor effects of the treatment with CY and LPS in BCGtreated mice are mediated by the reduction of tumor burden by CY and a serum factor induced by LPS. Antitumor activity ; cyclophosphamide ; LPS ; BCG ; serum factorWe have observed that an injection of bacterial lipopolysaccharide retarded the growth of tumors inoculated subcutaneously in mice pretreated with BCG (Sato et al. 1986). The antitumor activity of LPS seemed to be mediated by a serum factor. However prolongation of survival time was not significant statistically. Because of toxicity and tolerance (Madonna and Vogel 1985), repeated injections of LPS are not feasible. There have been a number of reports dealing with the antitumor effect of chemotherapeutic agents in BOG-treated animals. However no publication is available concerning the antitumor activity of LPS in combination with anticancer drugs in mice pretreated with BOG. In this study,

show abstract

Section: Discussionmentioning

confidence: 99%

Antitumor activity of cyclophosphamide and lipopolysaccharide in tumor-bearing mice pretreated with BCG.

Sato

Itô

Abé

et al. 1987

Tohoku J. Exp. Med.

View full text Add to dashboard Cite

show abstract

“…The high doses (in humans >120 mg/kg, in mice >400 mg/kg) of drug required for effective chemotherapy cause immunosuppression. However, at low doses (in mice, <100 mg/kg), cyclophosphamide treatment results in enhanced immune responses against a variety of antigens (23)(24)(25)(26)(27), a property that was attributed to the ability to selectively kill Tregs (28)(29)(30)(31). In mouse experiments, it was shown that upon cyclophosphamide injection, the number of Tregs decreased by day 4.…”

Section: Introductionmentioning

confidence: 99%

Effect of Adenovirus-Mediated Heat Shock Protein Expression and Oncolysis in Combination with Low-Dose Cyclophosphamide Treatment on Antitumor Immune Responses

Paolo¹,

Tuve²,

Ni³

et al. 2006

Cancer Research

View full text Add to dashboard Cite

Heat shock proteins such as gp96 have the ability to chaperone peptides and activate antigen-presenting cells. In this study, we tested whether adenovirus-mediated overexpression of secreted or membrane-associated forms of gp96 in tumor cells would stimulate an antitumor immune response. Studies were carried out in C57Bl/6 mice bearing aggressively growing s.c. tumors derived from syngeneic TC-1 cells, a cell line that expresses HPV16 E6 and E7 proteins. We found that secreted gp96 can induce protective and therapeutic antitumor immune responses. Our data also indicate that the antitumor effect of sgp96 expression seems to be limited by the induction of suppressive regulatory T cells (Treg). TC-1 tumor transplantation increased the number of splenic and tumor-infiltrating Tregs. Importantly, treatment of mice with low-dose cyclophosphamide decreased the number of Tregs and enhanced the immunostimulatory effect of sgp96 expression. We also tested whether an oncolytic vector (Ad.IR-E1A/TRAIL), that is able to induce tumor cell apoptosis and, potentially, release cryptic tumor epitopes in immunogenic form, could stimulate antitumor immune responses. Although tumor cells infected ex vivo with Ad.IR-E1A/TRAIL had no antitumor effect when used as a vaccine alone, the additional treatment with low-dose cyclophosphamide resulted in the elimination of pre-established tumors. This study gives a rationale for testing approaches that suppress Tregs in combination with oncolytic or immunostimulatory vectors. (Cancer Res 2006; 66(2): 960-9)

show abstract

“…Low-dose CTX (200-300 mg m-2) given 2-4 days before antigen administration enhances humoral and cellular responses to vaccine immunisation in tumour-bearing animals (Glaser, 1979;Havas and Schiffmann, 1981) and in man (Berd et al, 1984;Fagerberg et al, 1995). It has been suggested that this effect is a result of inactivation of suppressor T-lymphocytes which downregulate responses to novel antigens (Bonavida et al, 1979;Berd and Mastrangelo, 1988).…”

mentioning

confidence: 99%

A randomised phase II study of sialyl-Tn and DETOX-B adjuvant with or without cyclophosphamide pretreatment for the active specific immunotherapy of breast cancer

Miles

Towlson²,

Graham³

et al. 1996

Br J Cancer

104

View full text Add to dashboard Cite

Summary Studies in animal models of mouse mammary carcinoma have shown that ovine submaxillary mucin, which carries multiple sialyl-Tn (STn) epitopes, is effective in stimulating an immune response and inhibiting tumour growth. In similar studies using carbohydrate antigens, pretreatment with low-dose cyclophosphamide has been shown to be important in modulating the immune response to antigen possibly by inhibiting suppresser T-cell activity. In a clinical trial assessing the efficacy and toxicity of synthetic STn, patients with metastatic breast cancer were randomised to receive 100 ug STn linked to keyhole limpet haemocyanin (KLH) with DETOX-B adjuvant given by subcutaneous injection at weeks 0, 2, 5 and 9 with or without low-dose cyclophosphamide (CTX, 300 mg m2) pretreatment, 3 days before the start of immunotherapy. Patients with responding or stable disease after the first four injections were eligible to receive STn-KLH at 4 week intervals. The main toxicity noted was the development of subcutaneous granulomata at injection sites. Of 23 patients randomised, 18 received four injections, 5 patients having developed progressive disease during the initial 12 week period. Two minor responses were noted in the 18 patients who received four active specific immunotherapy (ASI) injections and a further five patients had stable disease. Six patients continued ASI at 4 week intervals and a partial response was noted in a patient who had previously had stable disease. All patients developed IgG and IgM responses to sialyl-Tn and levels of IgM antibodies were significantly higher in those patients who were pretreated with CTX. Measurable tumour responses have been recorded following ASI with STn-KLH plus DETOX and the immunomodulatory properties of low-dose CTX have been confirmed.

show abstract

Augmentation of specific immune response against a syngeneic SV40-induced sarcoma in mice by depletion of suppressor T cells with cyclophosphamide

Cited by 50 publications

References 24 publications

Antitumor activity of cyclophosphamide and lipopolysaccharide in tumor-bearing mice pretreated with BCG.

Antitumor activity of cyclophosphamide and lipopolysaccharide in tumor-bearing mice pretreated with BCG.

Effect of Adenovirus-Mediated Heat Shock Protein Expression and Oncolysis in Combination with Low-Dose Cyclophosphamide Treatment on Antitumor Immune Responses

A randomised phase II study of sialyl-Tn and DETOX-B adjuvant with or without cyclophosphamide pretreatment for the active specific immunotherapy of breast cancer

Contact Info

Product

Resources

About