Mantle cell lymphoma has a poor long-term prognoses. High dose chemotherapy with stem cell transplant prolongs survival, but chemotherapy-resistant lymphoma cells persist, and ultimately cause patients to relapse and succumb to disease. Targeting those few chemotherapy-resistant cells with an alternate modality -such as immunotherapy- might prevent or delay relapse. We have developed a maneuver - 'immunotransplant'-which accomplishes this by sequencing: vaccination, T-cell harvest, and myeloablation followed by T-cell re-infusion. Pre-clinically, immunotransplant amplifies vaccine-induced anti-tumor T cell responses and cures large, myeloablation-resistant tumors. We initiated a clinical trial and have now demonstrated that -as in the animal model- immunotransplant amplifies vaccine-induced anti-tumor T cell responses. Going forwards, we now have an opportunity to increase the size of our cohort to study whether: 1) immunotransplant improves clinical responses compared to recent studies of standard transplant, 2) whether certain functional profiles of anti-tumor T cell response predict clinical efficacy (e.g. cytokineproducing CD4 T cells versus perforin-producing CD8 T cells), 3) features of vaccine- or immunotransplant-induced T-cell repertoire skewing (as determined by TCRbV high throughput sequencing) correlate with either functional anti-tumor T cell profiles or clinical outcomes (towards developing an """"""""off-the-shelf immune assay).
Mantle cell lymphoma is currently incurable. High dose chemotherapy with stem cell transplant prolongs survival, but patients eventually relapse. We developed a maneuver combining stem cell transplant with a patient-specific vaccine, using the immune system to eliminate lymphoma cells that persist post-transplant. Our first 9 patients have shown that 'immunotransplant'does induce a tumor-reactive Immune system. We can now discover whether patients have better clinical outcomes.
| Kohrt, Holbrook E; Houot, Roch; Marabelle, Aurélien et al. (2012) Combination strategies to enhance antitumor ADCC. Immunotherapy 4:511-27 |
