Autologous tumor cell vaccine induces antitumor T cell immune responses in patients with mantle cell lymphoma: A phase I/II trial

Matthew J. Frank, Michael S. Khodadoust, Debra K. Czerwinski, Ole A.W. Haabeth, Michael P. Chu, David B. Miklos, Ranjana H. Advani, Ash A. Alizadeh, Neel K. Gupta, Lauren S. Maeda, Sunil A. Reddy, Ginna G. Laport, Everett H. Meyer, Robert S. Negrin, Andrew R. Rezvani, Wen Kai Weng, Kevin Sheehan, Malek Faham, Ami Okada, A. Holliston MooreDestiny L. Phillips, Irene L. Wapnir, Joshua D. Brody, Ronald Levy

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26 Scopus citations

Abstract

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.

Original languageEnglish
Article numbere20191712
JournalJournal of Experimental Medicine
Volume217
Issue number9
DOIs
StatePublished - 7 Sep 2020

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