Allogeneic hematopoietic cell transplantation as immunotherapy for solid tumors: current status and future directions.
Although myeloablative conditioning can cytoreduce or debulk malignancies, the curative antitumor effects of allogeneic hematopoietic stem cell transplantation (HCT) are mostly mediated by transplanted donor immune cells. A heightened awareness and appreciation of the immune-mediated anticancer effects that occur after allogeneic transplantation has led to the increasing use of reduced-intensity stem cell transplantation (RIST) approaches to treat advanced malignancies. The graft-versus-leukemia effects that occur against hematologic cancers after RIST have recently attracted oncologists to explore the therapeutic potential of allogeneic HCT for treatment-refractory solid tumors. Delayed tumor regression after RIST in a subset of patients with metastatic renal cell, breast, ovarian, pancreatic, and colon carcinoma has recently been reported, confirming the existence of a graft-versus-tumor effect in solid tumors. Advanced disease states, rapidly growing tumors, and accrual of patients with extremely short survival are factors that have been identified to limit the efficacy of allogeneic immunotherapy. This review discusses results of allogeneic HCT for solid tumors and the development of newer transplant strategies to optimize the potential of the graft-versus-tumor effect.
Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1652, USA.
Andreas
A
Lundqvist
Richard
R
Childs
D001943:Breast Neoplasms / Q000276:immunology / Q000628:therapy; D002292:Carcinoma, Renal Cell / Q000276:immunology / Q000628:therapy; D002986:Clinical Trials as Topic; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology; D020544:Graft vs Leukemia Effect / Q000276:immunology; D020350:Graft vs Tumor Effect / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D016233:Immunotherapy, Active; D016219:Immunotherapy, Adoptive / Q000639:trends*; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous