Submitted May 29, 2008
Accepted July 27, 2008
Immunotransplant preferentially expands Teffector cells over Tregulatory cells and cures large lymphoma tumors
Joshua D Brody, Matthew J Goldstein, Debra K Czerwinski, and Ronald Levy*
Division of Oncology, Department of Medicine, Stanford University Medical Center, Stanford, CA, United States
* Corresponding author; email: levy{at}stanford.edu.
Ex vivo expanded tumor-infiltrating lymphocytes infused into lymphodepleted recipients has clear anti-tumor efficacy. More practical sources of such anti-tumor lymphocytes would broaden the application of this approach.
Previously, we described an in situ vaccination combining chemotherapy with intra-tumoral injection of CpG-enriched oligonucleotides, which induced T-cell immunity against established lymphoma. An ongoing clinical trial of this maneuver has demonstrated clinical responses in lymphoma patients.
Here, we use this vaccine maneuver to generate immune cells for transfer into irradiated, syngeneic recipients. Transferred tumor-specific Teffector cells preferentially expanded, increasing the Teffector:Treg ratio in these 'immunotransplant' recipients, and curing large and metastatic tumors. Donor T cells were necessary for tumor protection and CD8 T cell immune responses were enhanced by post-transplant booster vaccination.
Hematopoietic stem cell transplant is a standard therapy for lymphoma. Therefore, in situ tumor vaccination followed by immunotransplant of harvested tumor-specific T cells could be directly tested in clinical trials to treat otherwise resistant malignancies.
