1. Autologous tumor cell vaccine induces antitumor T cell immune responses in patients with mantle cell lymphoma: A phase I/II trial
- Author
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Ash A. Alizadeh, Kevin Sheehan, Neel K. Gupta, Debra K. Czerwinski, Malek Faham, Ole Audun Werner Haabeth, Andrew R. Rezvani, Ginna G. Laport, Michael P. Chu, Matthew J. Frank, Irene Wapnir, Sunil Reddy, Michael S. Khodadoust, Everett Meyer, Robert S. Negrin, Ami Okada, David B. Miklos, Ranjana H. Advani, Joshua Brody, Destiny L Phillips, Lauren S. Maeda, Ronald Levy, A Holliston Moore, and Wen-Kai Weng
- Subjects
Adult ,Male ,Adoptive cell transfer ,Neoplasm, Residual ,Endpoint Determination ,T-Lymphocytes ,T cell ,Immunology ,Kaplan-Meier Estimate ,Lymphoma, Mantle-Cell ,CD8-Positive T-Lymphocytes ,Cancer Vaccines ,Transplantation, Autologous ,B7-H1 Antigen ,Article ,Autologous stem-cell transplantation ,hemic and lymphatic diseases ,Cell Line, Tumor ,Autologous Tumor Cell Vaccine ,medicine ,Humans ,Immunology and Allergy ,Cytotoxic T cell ,Aged ,business.industry ,Immunity ,Middle Aged ,medicine.disease ,Minimal residual disease ,Transplantation ,Leukemia & Lymphoma ,Treatment Outcome ,medicine.anatomical_structure ,Oligodeoxyribonucleotides ,Tumor immunology ,Cancer research ,Female ,Mantle cell lymphoma ,business ,Immunologic Memory - Abstract
A CpG-stimulated autologous tumor cell vaccine for patients with MCL is safe and feasible and induces detectable antitumor T cell immune responses. Patients who received the CpG-MCL vaccination demonstrated freedom from MRD at 1 yr after ASCT that surpassed previously reported rates., 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.
- Published
- 2020