Analysis of synergy between cyclophosphamide Therapy and Immunity Against a Mouse Tumour

Chassoux, D.; Gotch, F; MacLennan, I. C. M.

doi:10.1038/bjc.1978.190

Cited by 21 publications

(3 citation statements)

References 16 publications

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“…The effectiveness of chemotherapy was decreased when tumor-bearing animals were immunosuppressed with antithymocyte serum [11,14,26], x-irradiation [16,26,31], or high doses of drug [17,31]. The effectiveness of chemotherapy was increased in the presence of antitumor immunity developed by preimmunizing the tumor-bearing animals [5,17] or by adoptively transferring immunity with lymphoid cells [7,11,12,18,21,23]. Several mechanisms have been suggested for cooperation between chemotherapy and host antitumor immunity.…”

Section: Introductionmentioning

confidence: 99%

“…Reprint requests should be sent to S. Dray (a) reduce the tumor burden to a level whereby existent host antitumor immunity can eliminate residual tumor cells [5]; (b) slow tumor growth long enough to allow the development of potent host antitumor immunity [5]; (c)render residual tumor cells more immunogenic, thereby providing a superior stimulation for the development of host antitumor immunity [2,8,9]; (d)render residual tumor cells more susceptible to immune lysis [4]; or (e) eliminate suppressor cells [14,23], thereby allowing the generation and/or expression of potent host antitumor immunity [14].…”

Section: Introductionmentioning

confidence: 99%

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Increase in the effectiveness of melphalan therapy with progression of MOPC-315 plasmacytoma tumor growth

Ben-Efraim

Bocian

Mokyr

et al. 1983

Cancer Immunol Immunother

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Following inoculation with 1 X 10(6) MOPC-315 tumor cells, a single injection of a very low dose of melphalan (L-PAM, L-phenylalanine mustard), 0.75 mg/kg, cured most of the mice bearing a day 11 large primary tumor (20 mm) and metastases, but failed to cure mice bearing a day 4 nonpalpable tumor. Treatment of mice bearing a nonpalpable tumor with the very low dose of drug compromised the ability of the mice to respond effectively to the same low dose of drug when the tumor became large (day 12). However, a nonpalpable tumor could be eradicated by treatment of tumor bearers with a low dose of L-PAM, if it was present concomitantly with a large tumor on the contralateral side. A high dose of L-PAM, 15 mg/kg, cured mice bearing either a nonpalpable or a large tumor. The eradication of the tumor induced by the high dose of L-PAM appeared to be due solely to the tumoricidal effect of the drug. On the other hand, the eradication of the tumor by the low dose of L-PAM also required the participation of antitumor immunity of the host, since subsequent injection of antithymocyte serum abrogated the curative effect of the drug in most mice. Mice cured by a high dose of L-PAM were not resistant to subsequent lethal tumor challenge. In contrast, mice cured by the low dose of L-PAM were able to reject a tumor challenge of 300 times the minimal lethal tumor dose. The results obtained with L-PAM therapy are similar to the results that we had previously reported with cyclophosphamide therapy. Thus, the timing of therapy with a low dose of drug for mice bearing a MOPC-315 tumor is critical for successful therapy. Moreover, the selection of a low dose rather than a high dose of drug to eradicate a large tumor offers the advantage that it results in long-lasting potent antitumor immunity as a consequence of the participation of host antitumor immunity in the eradication of the tumor.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Increase in the effectiveness of melphalan therapy with progression of MOPC-315 plasmacytoma tumor growth

Ben-Efraim

Bocian

Mokyr

et al. 1983

Cancer Immunol Immunother

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“…The cooperation between the effect of the drug and the antitumor immune response was explained either by a change in the kinetics of tumor development induced by chemotherapy [4] or by the selective elimination of various suppressor cell populations by chemotherapeutic agents. In this respect, it was shown that cyclophosphamide (CY) acted selectively against suppressor T cells involved in cell-mediated immune responses in mice [7,9,14], increased T-cell-mediated immunity in cancer patients [11], and inhibited the generation of nonspecific human suppressor cells by ConA [8,15].…”

Section: Introductionmentioning

confidence: 99%

In vitro selective effect of melphalan on human T-cell populations

Ben-Efraim

Komlos

Notmann

et al. 1985

Cancer Immunol Immunother

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In vitro treatment with 2 micrograms/2 X 10(6) cells melphalan (L-PAM: L-phenylalanine mustard) significantly decreased the total number of T lymphocytes from peripheral blood (PBL) of healthy human donors and of the OKT4 population (precursor suppressor/helper/inducer) T cells as defined by monoclonal antibodies OKT3 and OKT4, respectively. No changes in the OKT+8 lymphocyte population (cytotoxic/mature suppressor cells) were observed following the same treatment. Preincubation of PBL with L-PAM at concentrations that do not affect the rate of DNA synthesis in PHA-stimulated lymphocytes inhibited the generation of T suppressor lymphocytes by ConA, as shown by their effect on PHA stimulation. Treatment of allogeneic PBL with L-PAM had no effect on mature suppressor T cells already induced by ConA, as shown by incubation of PBL with L-PAM after incubation with ConA.

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Effects on metastases of drug therapy during developing and established tumor immunity

Vaage

Costanza

1983

Intl Journal of Cancer

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The effectiveness of treatment with cyclophosphamide, methotrexate and 5-fluorouracil was studied during the s.c. and pulmonary growth of syngeneic C3H/He mammary carcinomas. Treatments with cyclophosphamide, methotrexate and 5-fluorouracil during the primary induction of immunity against a mouse mammary carcinoma inhibited the growth of the tumor, but also inhibited the development of an effective immune resistance against subsequent implants of the same tumor. However, drug treatments of mice with established tumor immunity gave added benefit without detectable depression of immune resistance.

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Analysis of synergy between cyclophosphamide Therapy and Immunity Against a Mouse Tumour

Cited by 21 publications

References 16 publications

Increase in the effectiveness of melphalan therapy with progression of MOPC-315 plasmacytoma tumor growth

Increase in the effectiveness of melphalan therapy with progression of MOPC-315 plasmacytoma tumor growth

In vitro selective effect of melphalan on human T-cell populations

Effects on metastases of drug therapy during developing and established tumor immunity

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