التفاصيل البيبلوغرافية
| العنوان: |
Impact of CTLA-4 blockade in conjunction with metronomic chemotherapy on preclinical breast cancer growth. |
| المؤلفون: |
Parra, Karla1, Valenzuela, Paloma1, Lerma, Natzidielly1, Gallegos, Alejandra1, Reza, Luis C1, Rodriguez, Georgialina1, Emmenegger, Urban2, Di Desidero, Teresa3, Bocci, Guido3, Felder, Mitchell S4, Manciu, Marian5, Kirken, Robert A1, Francia, Giulio1 |
| المصدر: |
British Journal of Cancer. 1/31/2017, Vol. 116 Issue 3, p324-334. 11p. 8 Graphs. |
| مستخلص: |
Background: Although there are reports that metronomic cyclophosphamide (CTX) can be immune stimulating, the impact of its combination with anti-CTLA-4 immunotherapy for the treatment of cancer remains to be evaluated.Methods: Murine EMT-6/P breast cancer, or its cisplatin or CTX-resistant variants, or CT-26 colon, were implanted into Balb/c mice. Established tumours were monitored for relative growth following treatment with anti-CTLA-4 antibody alone or in combination with; (a) metronomic CTX (ldCTX; 20 mg kg-1 day-1), b) bolus (150 mg kg-1) plus ldCTX, or (c) sequential treatment with gemcitabine (160 mg kg-1 every 3 days).Results: EMT-6/P tumours responded to anti-CTLA-4 therapy, but this response was less effective when combined with bolus plus ldCTX. Anti-CTLA-4 could be effectively combined with either ldCTX (without a bolus), or with regimens of either sequential or concomitant gemcitabine, including in orthotopic EMT-6 tumours, and independently of the schedule of drug administration. Tumour responses were confirmed with CT-26 tumours but were less pronounced in drug-resistant EMT-6/CTX or EMT-6/DDP tumour models than in the parent tumour. A number of tumour bearing mice developed spontaneous metastases under continuous therapy. The majority of cured mice rejected tumour re-challenges.Conclusions: Metronomic CTX can be combined with anti-CTLA-4 therapy, but this therapy is impaired by concomitant bolus CTX. Sequential therapy of anti-CTLA-4 followed by gemcitabine is effective in chemotherapy-naive tumours, although tumour relapses can occur, in some cases accompanied by the development of spontaneous metastases. [ABSTRACT FROM AUTHOR] |
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