Ivan M. Borrello, MD, Eduardo M. Sotomayor, MD

Abstract and Introduction
Abstract
Background. Improvements in the identification of tumor-associated antigens and in our understanding of the mechanisms regulating antitumor immune responses have revived interest in the use of therapeutic cancer vaccination. Due to their unique characteristics, hematologic malignancies represent an ideal target for vaccinebased therapeutic interventions.
Methods. A review of published vaccine studies in experimental models as well as the results of clinical trials using vaccines for patients with hematologic tumors is presented.
Results. Tumor vaccine strategies can be divided into two categories: antigen-specific strategies, in which the tumor antigens have been identified and can be isolated to develop a molecularly defined vaccine, and cellular or non-antigen-specific, in which the tumor-specific antigens are unknown but presumed to exist within the material used to generate the vaccine. Early clinical trials have shown not only the feasibility and safety of either approach but also the obstacles in therapeutic cancer vaccination as an effective treatment modality for hematologic malignancies.
Conclusions. Active immunization using current cancer vaccine approaches is feasible and safe. Although no major successes have been reported, the positive clinical results observed in some patients support the potential for therapeutic cancer vaccination in the management of hematologic malignancies. Results of studies that are testing vaccine formulations, targets, and settings (eg, bone marrow transplantation) may support the use of cancer vaccination as an efficient therapeutic strategy against tumors of hematologic origin.

Introduction
The past several years have witnessed a significant progress in the treatment of hematologic malignancies. This improvement has been largely the result of newer and more effective combination chemotherapy, improved radiation delivery, and the major impact conferred by bone marrow transplantation (BMT). In spite of these successes, a significant portion of patients with hematologic tumors will ultimately die of their disease. In recent years, therefore, much attention has been given to identify novel non-cross-resistant therapeutic strategies that may positively affect the management of these diseases.^[1,2]

A growing body of evidence suggests that immunemediated mechanisms may aid in the killing of malignant cells in patients with hematologic malignancies. Indeed, the potential of the immune system to favorably affect the management of patients harboring hematologic tumors has been highlighted by the reduced relapse rates observed in the allogeneic transplant setting compared with those of autologous BMT,^[3] the dramatic clinical benefit achieved with donor lymphocyte infusions (DLIs),^[4] and the recent clinical successes of antibody-based therapies for the treatment of non- Hodgkin's lymphomas.^[5] These clinical observations, together with the recent demonstration that cells of the immune system are capable to destroy chemotherapyresistant chronic myelogenous leukemia (CML) and multiple myeloma cell lines,^[6,7] have led to the development of novel immunotherapeutic strategies against cancers of hematologic origin. Among these strategies, active immunization with cancer vaccines is emerging as a valuable tool to harness the immune system against antigens expressed by these tumors.

In light of the evolving role of cancer vaccines in the treatment of hematologic malignancies, this article reviews the preclinical studies as well as the results of recently completed clinical trials using these approaches. Furthermore, we will discuss the obstacles that must be overcome to increase the efficacy of cancer vaccines for hematologic malignancies in the foreseeable future.

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Ivan M. Borrello, MD, and Eduardo M. Sotomayor, MD, Department of Oncology at the Johns Hopkins University School of Medicine, Baltimore, Md (IMB), and the Hematologic Malignancies Program, H. Lee Moffitt Cancer Center & Research Institute at the University of South Florida, Tampa, Fla (EMS).

Cancer Control 9(2):138-151, 2002. © 2002 H. Lee Moffitt Cancer Center and Research Institute, Inc