Cellular Vaccine Approaches

Abstract

Therapeutic cancer vaccines aim to generate immunologic targeting of cancer cells through the induction of effective cellular and antibody-mediated responses specific for antigens selectively expressed by the tumor. Exploiting the adaptive immune system as a targeted tool against cancer is appealing in its capacity for exact specificity and avoidance of unintended tissue damage seen by other conventional agents such as chemotherapy. There are a multitude of challenges to designing effective vaccine strategies. The components of a vaccine strategy start with the challenges of selecting immunogenic, tumor-specific antigen targets, choosing a platform with which to deliver the antigens, and enhancing the immunostimulatory context in which the vaccines are delivered. Although understanding the components of effective T-cell activation is essential, successful effector T cells can only be produced if there is also an understanding of the natural processes that tumors exploit to down-modulate active immune responses. These processes are normally used to down-regulate excessive tissue-destructive immune responses against infectious agents once the infecting agent is cleared or to prevent autoimmunity. Advances in molecular and cellular technologies continue to provide insights into the regulation of immune responses both to infectious agents and to cancer that may be manipulated to tip the balance in favor of tumor regression over immune tolerance. This review focuses primarily on cellular vaccines. For the purpose of this review, cellular vaccines are defined as vaccines that use whole cells or cell lysates either as the source of antigens or the platform in which to deliver the antigens. Dendritic cell (DC)-based vaccines focus on ex vivo antigen delivery to DCs. Other platforms such as GVAX (tumor cells genetically engineered to produce granulocyte-macrophage colony-stimulating factor) aim to deliver tumor antigens in vivo in an immune stimulatory context to endogenous DCs. Because data continue to emerge regarding the importance of the maturation status of DCs and the importance of the particular subset of DCs being targeted, these insights will be integrated into vaccine strategies that are likely to produce more effective vaccines.

Cytotoxic T cells and Cancer Therapy

“…Tumorvaccination in case of advanced stages of tumorproves to be relatively ineffective; but in patients with sub-advanced malignancies suitable vaccines can be of much effectiveness (with minimal residual disease). Tumor vaccination can be employed in association with other therapeutic modalities as proven to be effective in case of promyelocytic leukaemia (Padua et al, 2003;Le et al, 2010). Also, multivalent vaccines against tumors may be a viable approach as they prime CTLs to target multiple epitopes (Graff-Dubois et al, 2002).…”

Harnessing the Immune System to Fight Cancer: The Promise of Genetic Cancer Vaccines

“…DCs have been loaded with tumour antigens in the form of peptides, proteins, tumour lysates, and mRNAs. Alternatively, they have been fused with tumour cells or infected with viral vectors encoding tumourassociated antigens (reviewed in Le et al, 2010). Clinical development of DC-based cancer vaccines has several aspects that make this technology not ideal for application on a large scale.…”

Properties of bcr-abl-transformed mouse 12B1 cells secreting interleukin-2 and granulocyte-macrophage colony-stimulating factor: I. Derivation, genetic stability, oncogenicity and immunogenicity

“…Both autologous and allogenic cell vaccines are under consideration (17,19). Favourable results have been obtained in postremission acute myeloid leukaemia patients with a vaccine composed of a mixture of autologous cells and K562 cells, i.e.…”

“…GM-CSF secreted by gene-engineered tumour cells has been found to be the most potent stimulatory factor among the ten cytokines tested (15) and it has since become the most frequently used cytokine in the construction of cell-based cancer vaccines. GM-CSF secreting vaccines have been used in numerous preclinical and clinical studies, for reviews see (16)(17)(18).…”