Dendritic cell cancer vaccines: from the bench to the bedside.

Tamar Katz,Noam Benyamini,Irit Avivi,David Avigan,Jacalyn Rosenblatt

doi:10.5041/rmmj.10158

Abstract

The recognition that the development of cancer is associated with acquired immunodeficiency, mostly against cancer cells themselves, and understanding pathways inducing this immunosuppression, has led to a tremendous development of new immunological approaches, both vaccines and drugs, which overcome this inhibition. Both “passive” (e.g. strategies relying on the administration of specific T cells) and “active” vaccines (e.g. peptide-directed or whole-cell vaccines) have become attractive immunological approaches, inducing cell death by targeting tumor-associated antigens. Whereas peptide-targeted vaccines are usually directed against a single antigen, whole-cell vaccines (e.g. dendritic cell vaccines) are aimed to induce robust responsiveness by targeting several tumor-related antigens simultaneously. The combination of vaccines with new immuno-stimulating agents which target “immunosuppressive checkpoints” (anti-CTLA-4, PD-1, etc.) is likely to improve and maintain immune response induced by vaccination.

Highlights

In a large proportion of patients, hematological malignancies remain incurable with conventional chemotherapy
Similar promising results obtained in several other studies led to the use of bacilli Calmette–Guérin (BCG) for cancer immunotherapy, which continues to be employed to the present day as an effective therapy against superficial bladder cancer.[2] found to be at an increased risk of developing posttransplant lymphoproliferative disorders (PTLD),[9] and discontinuation of immunosuppressive drugs potentially resulting in immunity reconstruction could contribute to successful management of these patients
Another suppressive subset of cells is the heterogeneous population of myeloid-derived suppressor cells (MDSC) that are expanded in cancer and have the capacity to suppress the immune response; MDSC are generated in the bone marrow in response to cancer-derived factors and are recruited to the tumor site by CCL2, CXCL12, and CXCL5.40 The MDSCs suppress the activation of T effector and natural killer cells and induce expansion of regulatory T cells (Tregs)

Summary

INTRODUCTION

In a large proportion of patients, hematological malignancies remain incurable with conventional chemotherapy. The earliest evidence for the role of the immune response against cancer cells was provided in the work by William Coley, who injected Streptococcus pyogenes to sarcoma patients in an effort to reproduce spontaneous remissions observed in cancer patients developing erysipelas Ten percent of these incurable non-resectable patients responded.[1] Similar promising results obtained in several other studies led to the use of bacilli Calmette–Guérin (BCG) for cancer immunotherapy, which continues to be employed to the present day as an effective therapy against superficial bladder cancer.[2] found to be at an increased risk of developing posttransplant lymphoproliferative disorders (PTLD),[9] and discontinuation of immunosuppressive drugs potentially resulting in immunity reconstruction could contribute to successful management of these patients. One of the earliest and most successful immunotherapies developed for hematological malignancies was hematopoietic stem cell transplantation (HSCT) While this procedure is associated with significant morbidity and mortality, it has been shown to prolong long-term disease-free survival as well as overall survival and can be curative in a subset of patients. Studies in humans reported a high incidence of lymphomas and other malignancies in immunocompromised states.[7,8] Patients undergoing solid organ or bone marrow transplantation were

PRIMARY MECHANISMS OF IMMUNE ESCAPE

Regulatory Immune Cells

SINGLE ANTIGEN APPROACHES

VACCINATION IN CONJUNCTION WITH AUTOLOGOUS TRANSPLANTATION

Findings

IMMUNOMODULATORY THERAPY AND VACCINATION