Journal
NATURE CLINICAL PRACTICE ONCOLOGY
Volume 3, Issue 12, Pages 668-681Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ncponc0666
Keywords
adoptive cell transfer; immunodepletion; lymphodepletion; melanoma; T lymphocytes
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Funding
- Intramural NIH HHS [Z99 CA999999, Z01 BC010763-01] Funding Source: Medline
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In a recent clinical trial involving patients with metastatic melanoma, immunosuppressive conditioning with fludarabine and cyclophosphamide resulted in a 50% response rate in robust long-term persistence of adoptively transferred T cells. Experimental findings indicate that lymphodepletion prior to adoptive transfer of tumor-specific T lymphocytes plays a key role in enhancing treatment efficacy by eliminating regulatory T cells and competing elements of the immune system ('cytokine sinks'). Newly emerging animal data suggest that more profound lymphoablative conditioning with autologous hematopoetic stem-cell rescue might further enhance treatment results. Here we review recent advances in adoptive immunotherapy of solid tumors and discuss the rationale for lymphodepleting conditioning. We also address safety issues associated with translating experimental animal results of total lymphoid ablation into clinical practice.
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