1区 · 医学
Article
作者: Maeda, Lauren S. ; Miklos, David B. ; Moore, A. Holliston ; Haabeth, Ole A.W. ; Phillips, Destiny L. ; Weng, Wen-Kai ; Chu, Michael P. ; Frank, Matthew J. ; Advani, Ranjana H. ; Faham, Malek ; Brody, Joshua D. ; Czerwinski, Debra K. ; Negrin, Robert S. ; Khodadoust, Michael S. ; Okada, Ami ; Alizadeh, Ash A. ; Wapnir, Irene L. ; Meyer, Everett H. ; Sheehan, Kevin ; Reddy, Sunil A. ; Laport, Ginna G. ; Gupta, Neel K. ; Rezvani, Andrew R. ; Levy, Ronald
Here, we report on the results of a phase I/II trial (NCT00490529) for patients with mantle cell lymphoma who, having achieved remission after immunochemotherapy, were vaccinated with irradiated, CpG-activated tumor cells. Subsequently, vaccine-primed lymphocytes were collected and reinfused after a standard autologous stem cell transplantation (ASCT). The primary endpoint was detection of minimal residual disease (MRD) within 1 yr after ASCT at the previously validated threshold of ≥1 malignant cell per 10,000 leukocyte equivalents. Of 45 evaluable patients, 40 (89%) were found to be MRD negative, and the MRD-positive patients experienced early subsequent relapse. The vaccination induced antitumor CD8 T cell immune responses in 40% of patients, and these were associated with favorable clinical outcomes. Patients with high tumor PD-L1 expression after in vitro exposure to CpG had inferior outcomes. Vaccination with CpG-stimulated autologous tumor cells followed by the adoptive transfer of vaccine-primed lymphocytes after ASCT is feasible and safe.