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Successful Immunotherapy of HCMV Disease Using Virus-Specific T Cells Expanded from an Allogeneic Stem Cell Transplant Recipient
American Journal of Transplantation, 11/18/09

Hill GR et al. – The authors demonstrate for the first time, the successful expansion of HCMV–specific T cells from a seropositive transplant recipient of a seronegative graft with active HCMV disease and the long–term reconstitution of protective antiviral immunity following their adoptive transfer back into the patient.

Exclusive Author Commentary
Rajiv Khanna, 11/18/09

Although previous studies have demonstrated that it is possible to expand virus-specific T-cells from SCT donors, it has been thought that such an expansion would be improbable in SCT recipients of seronegative grafts. However, the data presented in this study demonstrate that it is indeed possible to activate a potent T response from SCT recipients who receive grafts from seronegative donors. One of the critical aspects of this work was that whilst this patient had circulating HCMV-specific T cells as a result of previous HCMV reactivations; they were largely non-functional. We emphasize that this is the first report in the literature where anergic HCMV-specific T cells from the SCT recipient have been expanded and rendered functional such that they successfully eradicate otherwise terminal HCMV disease. The success seen in this case contrasts failed attempts in solid organ setting where IFN?-producing T cells were specifically selected and the recipient remained on Tacrolimus whilst receiving adoptive T cell therapy. We now hope to confirm our findings in a formal clinical trial using a panel of 26 HLA class I and class II-restricted peptide epitopes which will include at least two HLA allele in >98% of the population. We believe this case represents a paradigm shift in our understanding of HCMV disease and its treatment after allogeneic SCT. These findings have important implications for the use of adoptive immunotherapy which has been previously thought to be unavailable to this group of transplant recipients.

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