[Frontiers in Bioscience 17, 635-655, January 1, 2012]

Enhancing graft-versus-leukemia after transplant: the rise of anti-cancer vaccines

Ana Brusic1,2, Catherine J. Wu1,3,4

1Cancer Vaccine Center, Dana-Farber Cancer Institute, Boston, MA, 2Monash University, Melbourne, Australia, 3Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, 4Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA

TABLE OF CONTENTS

1. Abstract
2. Reconstitution of donor immunity following HSCT offers a unique opportunity to apply cancer vaccines to expand anti-tumor immunity
3. Using responses in the post-transplant setting to discover immunogenic tumor antigens
3.1. T cell-based tumor antigen discovery
3.2. B cell expression library cloning
3.3. The bioinformatics approach to antigen discovery
3.4. Summary
4. Novel post-transplant interventions to enhance anti-leukemia responses: reconstitution-associated therapies
5. Novel post-transplant interventions to enhance anti-leukemia responses: anti-cancer vaccines
5.1. Defined antigen vaccines
5.2. Whole tumor cell vaccines
6. Novel adjuvants to enhance post-transplant vaccines
6.1. GM-CSF
6.2. TLR agonists
6.3. CD40L
7. Agents for checkpoint blockade to enhance post-transplant anti-tumor responses
7.1. Anti-CTLA4 blocking antibody
7.2. Anti-PD1/PDL1 antibody
7.3. Summary
8. Perspectives
9. Acknowledgements
10. References

1. ABSTRACT

Allogeneic hematopoietic stem cell transplantation (HSCT) remains the only truly effective curative treatment for refractory hematological malignancies. Unfortunately, relapse and transplant rejection continue to be of major concern. In order to enhance the effectiveness of the HSCT, various strategies have been explored to amplify the graft versus leukemia (GvL) effect. Cancer vaccines have emerged in recent years as a promising strategy for the immunotherapeutic treatment of cancer. Evidence shows that they are most likely to have the greatest effect in the setting of minimal residual disease and as adjuvant agents. With this in mind, researchers have begun to explore the use of cancer vaccines in conjunction with HSCT, with exciting results. There has also been recent work examining the effect of novel adjuvants or blockers of negative immune regulation to augment the effect of cancer vaccines in both the transplant and non-transplant settings. The addition of these agents may prove